Chapter 61: Arterial Occlusion

Acute limb ischemia requires rapid recognition and therapy for limb salvage. Critical limb ischemia occurs in chronic progressive peripheral arterial disease when pain at rest, ulceration, or gangrene exists. Despite improvements in the management of peripheral arterial disease, current 1-year mortality after the onset of critical limb ischemia is 25%, and 25% of survivors require amputation.^1,2

The prevalence of peripheral arterial disease (defined as an ankle-brachial index of <0.9) in the United States is 4.3% for those >40 years old and 15.5% for those >70 years old.³ This prevalence increases to 29% in high-risk populations in those >70 years old and those >50 years old with diabetes or a smoking history.⁴ In the elderly, both sexes are affected equally, although symptoms are present two to four times more commonly in men. Smoking and diabetes are the most important risk factors for arterial insufficiency.⁵ Additional risk factors include hyperlipidemia, hypertension, hyperhomocysteinemia, and an elevated C-reactive protein level.

Between 40% and 60% of patients with occlusive arterial disease have either coronary or cerebrovascular disease.⁶ The severity of peripheral vascular disease is closely linked to the risk of myocardial infarction, ischemic stroke, and death from vascular disease.⁷ The most frequently diseased arteries leading to limb ischemia are, in order of occurrence, the femoropopliteal, tibial, aortoiliac, and brachiocephalic vessels.

Acute limb ischemia results from a lack of blood supply to meet tissue oxygen and nutrient requirements. As time proceeds, cell death or irreversible tissue damage occurs. Peripheral nerves and skeletal muscle are more sensitive to ischemia, and irreversible changes occur in these tissues within 6 hours.

After restoration of the blood flow, reperfusion injury can occur, noted by the presence of muscle pain and swelling, renal failure, and peripheral muscle infarction. Often, hyperkalemia, myoglobinemia, metabolic acidosis, and an elevation in creatine kinase level exist. The extent of reperfusion injury depends on the duration and location of the arterial blockage, the amount of collateral flow, and the previous health of the involved limb. Approximately one third of all deaths from occlusive arterial disease are secondary to metabolic complications after revascularization.⁸

Disorders that can lead to arterial occlusion are compared in Table 61-1.

THROMBOSIS

Thrombotic occlusion is the most common cause of acute limb ischemia. Both native vessels and bypass grafts can thrombose. In the lower limbs, thrombotic occlusion accounts for >80% of cases.¹⁴ In the upper limbs, about half of all cases of acute limb ischemia are due to thrombosis, one third are due to embolism, and one fourth are secondary to arteritis.¹⁵ The distinction between a thrombosis and an embolism in any given patient is not always clear.

Nonembolic limb ischemia is secondary to atherosclerosis in most patients. Complete or high-grade obstruction occurs from plaque rupture or endothelial erosion followed by thrombus formation. Acute limb ischemia from plaque rupture obstructs flow completely, triggering symptoms. However, most nonembolic ischemia is characterized by chronic occlusion that may be clinically silent or muted depending on the collateral network.

Other than plaque rupture, progression of ischemic injury occurs through several mechanisms: (1) propagation of clot to occlude collateral vessels, (2) ischemia-related distal edema leading to high compartment pressures (compartment syndrome), (3) fragmentation of clot into the microcirculation, and (4) edema of the microvasculature cells. Large-vessel reperfusion may not resolve obstruction of the microvasculature.

Uncommonly, arterial thrombosis can develop in an apparently normal vessel without an atherosclerotic plaque; if seen, seek an underlying hypercoagulable condition. Subclinical vessel injury (from injections, catheters, or other mechanical events) or early atherosclerosis may still underlie these events.

EMBOLISM

Occlusion from embolism is less common than occlusion from thrombosis, in part due to the decline in the incidence of rheumatic heart disease and the treatment of atrial fibrillation with anticoagulants. Emboli originate from the heart in most cases. Atrial fibrillation is associated with at least two thirds of all peripheral emboli, and the clot most commonly originates in the left atrial appendage. The second most frequent source is a mural thrombus in the ventricle after recent myocardial infarction, accounting for about 20% of all limb emboli. Both atrial fibrillation and acute myocardial infarction predispose to poor cardiac wall motion and stagnant blood flow that promote clot formation. The mean time to development of a clot after myocardial infarction is 14 days (range, 3 to 28 days).¹⁶ The incidence of emboli originating from a mechanical valve has been lowered by advances in anticoagulation. Rare cardiac sources of emboli include tumor emboli from atrial myxomas, vegetations from valve leaflets, and parts of prosthetic cardiac devices.

Noncardiac sources of arterial emboli include thrombi from aneurysms and atheromatous plaques. Mural thrombi in aneurysms of aortoiliac, femoral, popliteal, and subclavian arteries are the most notable sources. Atheroemboli result from plaque fragmentation and cause obstruction of the microcirculation, producing symptoms in the hands, feet (blue toe syndrome), or cerebral circulation (transient ischemic attack). Atheroemboli consist of cholesterol-laden debris and platelet aggregates that can disseminate to multiple sites in the body. Paradoxical embolization can occur when a venous clot passes from the right to the left side of the heart through an intracardiac shunt, most commonly a patent foramen ovale.

The natural history of an embolus is either to fragment and embolize distally or to propagate locally into a larger clot. Two thirds of all noncerebral emboli enter vessels of the lower limbs and lodge where vessels branch or taper. The most common location for an embolus in the leg is the bifurcation of the common femoral artery, followed by the popliteal artery. In the upper limb, the brachial artery is the vessel most commonly affected by an embolism.

OTHER CAUSES

Intentional or accidental intra-arterial drug injections by medical personnel or those taking illicit drugs can result in local vasospasm, infectious arteritis, thrombosis, pseudoaneurysm, and mycotic aneurysm. Inert particles or drug crystals can embolize to obstruct end arteries, which can lead to gangrene of the digits. The prolonged use of vasopressor medications may result in arterial ischemia and occlusion, and their use requires close observation of extremity perfusion, particularly in patients with known pre-existing vascular disease.

Limb ischemia may also occur with nonembolic central causes. A thoracic aortic dissection can propagate into the subclavian and iliofemoral systems and present with neurologic and/or extremity findings. The false lumen created by the dissection occludes flow in the involved artery.

Patients with acute limb ischemia exhibit one or more of the "six Ps": pain, pallor, paralysis, pulselessness, paresthesias, and polar (for cold). A lack of one or more of these findings does not exclude ischemia. Furthermore, total occlusion of a severely diseased artery in patients with peripheral vascular disease with well-developed collateral blood supply may not be a dramatic event and can be silent. Pain alone may be the earliest symptom of ischemia, localized in the limb distal to the site of obstruction.

Skin changes include pallor first, followed by blotchy and mottled areas of cyanosis, and then associated petechiae and blisters. Late findings consist of skin and fat necrosis.

With vessel occlusion, severe and steady pain in the involved extremity associated with decreased skin temperature is common. Hypoesthesia or hyperesthesia due to ischemic neuropathy is typically an early finding, as is muscle weakness. Two-point discrimination, vibratory sensation, and proprioception are often diminished prior to the loss of deep sensation. Absence of a palpable distal pulse is not a particularly helpful sign in a patient with long-standing vascular disease unless accompanied by skin changes compatible with acute arterial obstruction. An abrupt loss of a previously strong pulse is suggestive of acute embolization.

As ischemic injury progresses, anesthesia and paralysis become evident and foreshadow impending gangrene and the loss of limb viability. Preservation of light touch on skin testing is a good guide to tissue viability. A patient with an acute ischemic limb with signs of muscle paralysis, sensory loss, and prolonged ischemia has a limb that is likely nonviable. The Rutherford criteria (Table 61-2) provide a more formal prognostic stratification of the clinical stages of acute limb ischemia.

The time limit for limb viability is dependent on the effectiveness of collateral circulation. Therefore, no arbitrary time period should be used to rule out treatment options despite the common belief that "treatment must occur in 4 to 6 hours."

Microemboli present clinically with pain and cyanosis in the involved digit, petechiae, and local muscle pain and tenderness at the site of infarction. Showering of these emboli creates several different small areas of involvement. Although mottling and decreased function may occur, pulses are preserved, assuming they were present to start, which is unusual in this population. Table 61-1 notes symptoms of related disorders.

ACUTE VERSUS CHRONIC ARTERIAL DISEASE

Acute limb ischemia is defined as symptoms starting within a 2-week period. Pain over the distal forefoot waking the patient at night or requiring the patient to hang his or her feet over the bed is suggestive of severe arterial occlusion and requires prompt consultation and treatment.

Claudication is a cramp-like pain, ache, or tiredness that is brought on by exercise and relieved by rest. It is reproducible, resolves within 2 to 5 minutes of rest, and recurs at consistent walking distances. The pain of acute limb ischemia is not well localized, is not relieved by rest or gravity, and can be a worsening of chronic pain (if it is caused by a thrombotic event).

Chronic obstructive arterial disease is characterized by intermittent claudication, which may progress to intermittent ischemic pain at rest. Femoropopliteal disease and aortoiliac disease often cause reproducible calf pain with activity that is relieved with rest. Pain at rest typically localizes to the foot and is aggravated by leg elevation, improves with standing, and is poorly controlled with analgesics. Classical teaching suggests that single-level disease in one of the segments noted in Table 61-3 may result in claudication, whereas multilevel disease results in rest pain or tissue loss. Table 61-3 lists symptom sites of commonly compromised arteries.

The pain associated with intermittent vascular claudication can be confused with leg pain from many causes (Table 61-4) including spinal stenosis or lumbosacral radiculopathy.

Uncommon presentations of deep venous thrombosis—phlegmasia cerulea dolens (painful blue inflammation) and phlegmasia alba dolens, or "milk leg"—can be confused with obstructive arterial disease. In phlegmasia cerulea dolens, the leg is markedly swollen and cyanotic from venous engorgement due to massive iliofemoral thrombosis. This high-grade obstruction can compromise perfusion to the foot from high compartment pressures and lead to venous gangrene.¹⁷ Phlegmasia alba dolens is usually seen during pregnancy and is a result of iliofemoral thrombosis with concomitant leg pallor from arterial spasm. Dorsalis pedis and posterior tibial pulses may be diminished or absent, which can lead to a false diagnosis of arterial occlusion. The arterial spasm with milk leg is transient and often followed by venous engorgement, which aids diagnosis. For a more complete list of the differential diagnoses for intermittent claudication, see Table 61-4.

On physical examination, examine the skin and all peripheral pulses of both extremities. Compare the unaffected to the affected limb. Shiny, hyperpigmented skin with hair loss and ulceration, thickened nails, muscle atrophy, vascular bruits, and poor pulses are the hallmark of chronic obstructive arterial disease. In contrast to the common medial malleolar location of venous insufficiency ulcers, arterial ulcers tend to occur on the foot and toes and are typically more painful. When evaluating someone with a chronic, nonhealing ulcer, consider the possibility of both venous and arterial insufficiency. Perform a cardiovascular and abdominal examination, including auscultation for bruits, search for murmurs, and palpation of the abdominal aorta.

The clinical exam guides initial decisions and causes (Table 61-5); if severe or limb-threating new ischemia of any cause is suspected, promptly consult a vascular surgeon prior to performing confirmatory imaging. Other features guide care; a history of an abruptly ischemic limb in a patient with atrial fibrillation or recent myocardial infarction strongly suggests an embolus. Acute ischemia in the limb of a patient known to have advanced obstructive arterial disease is more likely due to thrombosis or a low cardiac output state. In patients without antecedent claudication and a normal uninvolved limb, embolic occlusion is likely present. If there are ischemic changes, an arterial thrombotic cause is more likely than an embolism.

For a more detailed comparison of acute embolism and thrombosis, see Table 61-5.

Decreased perfusion is detected by blanching the involved extremity with finger pressure and noting a delay in the return of blood compared with the uninvolved extremity; 2 to 3 seconds is considered normal. The test is influenced by many other factors, so it alone cannot determine perfusion status.

Use a hand-held Doppler ultrasound device over pulse areas to detect presence or absence of blood flow and the amplitude. Approximately 10% of patients have only one pedal or ankle pulse present secondary to an anatomic variation. If Doppler flow is detected in the affected limb, check the ankle-brachial index and segmental leg pressures. The ankle-brachial index is the ratio of the systolic blood pressure with the cuff just above the malleolus (with the Doppler probe over the posterior tibial or dorsalis pedis artery) to the highest brachial pressure in either arm (Figure 61-1). Patients with chronic obstructive arterial disease have an ankle-brachial index of <0.9. Values of <0.25 suggest potentially limb-threatening vascular disease. An ankle-brachial index of >1.3 is likely secondary to a noncompressible vessel; it may be seen in patients with severe vascular calcification, especially diabetics, and is notoriously unreliable in this patient population. In such cases, toe-brachial pressures can be measured, but the technique requires specialized equipment. Segmental blood pressures measured with the Doppler device on the posterior tibial or dorsalis pedis artery and the cuff placed below the knee, above the knee, and on the high thigh can aid assessment. A difference of 30 mm Hg or more between any two adjacent levels localizes the site of obstruction. With successful reperfusion, the ankle-brachial index and segmental pressures begin to return to baseline or normalize if no residual obstruction remains after clot dissolution.

LABORATORY EVALUATION

Aside from seeking markers of cellular death (e.g., creatine kinase or myoglobin and serum lactate), obtain other tests to assess metabolic status (electrolytes and glucose), renal function (BUN and creatinine plus urinalysis), anemia and infection (CBC), and bleeding tendency (prothrombin and partial thromboplastin times). Levels of cardiac markers and ECG may identify associated cardiac triggers (including infarction or rhythm change).

IMAGING

If the diagnosis of arterial occlusion is in question, duplex US is very accurate for detecting complete or incomplete obstruction. Sensitivity declines for localization of thromboembolic occlusion at or below the calf level. Transthoracic cardiac echocardiography can help detect embolic sources, and transesophageal approaches add the ability to detect aortic root pathology.

Arteriography is often obtained prior to surgical intervention¹ or to direct therapy. Embolic occlusion displays an abrupt cutoff of blood flow in a disease-free or minimally diseased vessel. Arteriography requires the administration of contrast material, so assess renal function and hydrate before the study.

CT with contrast is the most readily available added study in the ED and has a sensitivity similar to that of conventional contrast studies in large vessels. MRI has higher sensitivity and specificity but is less readily available.

The objectives of therapy for acute arterial obstruction are restoration of blood flow to preserve limb and life, and prevention of recurrent thrombosis or embolism (Table 61-6).

IV unfractionated heparin (weight-based 80 units/kg bolus followed by an infusion of 18 units/kg/h) is common initial therapy. Anticoagulation may prevent clot extension, recurrent embolization, venous thrombosis, microthrombi distal to the obstruction, and reocclusion after reperfusion.¹⁹ It is still unclear whether heparin administration improves outcome in the clinical circumstance of thrombosis in a plaque-laden artery. Enoxaparin (1 milligram/kg SC) is an alternative, although heparin remains the common choice. Aspirin (325 milligrams in naïve patients) may enhance clot reduction through antiplatelet actions.

Even before starting anticoagulation, start seeking vascular consultation, transferring if needed. Stratifying patients with acute limb ischemia by Rutherford criteria (Table 61-1) can guide initial care. Patients with stage I and stage IIa limb ischemia may undergo diagnostic imaging workup prior to more definitive treatments. Patients with stage IIb ischemia often require immediate revascularization without additional diagnostic imaging modalities prior to operative or interventional treatment. Patients with stage III ischemia have suffered irreversible damage and likely require amputation. Provide adequate analgesia and fluid resuscitation and treat heart failure (if existing) to help improve limb perfusion.

The vascular surgeon determines definitive treatment, which can include catheter-directed thrombolysis, percutaneous mechanical thrombectomy, revision of an occluded bypass graft, and revascularization with either percutaneous transluminal angioplasty or standard surgery.^2,18 Catheter-directed intra-arterial thrombolysis is now often chosen over systemic thrombolysis for peripheral artery embolic or thrombotic disease.^18,19 In a subacute thrombotic occlusion with a well-developed collateral blood supply, medical management is common.

The longer-term nonsurgical management of chronic obstructive arterial disease focuses on the combination of smoking cessation, exercise, and pharmacotherapy. Daily aspirin (81 to 162 milligrams) reduces mortality by 25%.^{4,20, 21, 22, 23} Anticoagulants, such as warfarin, factor Xa, or thrombin inhibitors, are used when clot formation is severe or recurrent.²⁰ Lowering cholesterol and blood pressure and improving glycemic control also are key secondary modifiers.⁴

The American College of Cardiology/American Heart Association 2005 guidelines include cilostazol, a phosphodiesterase inhibitor, as a Class I recommendation for the treatment of claudication in patients with obstructive arterial disease² (avoid in patients with heart failure). Pentoxifylline is a second-line therapy for the treatment of claudication (Class IIb).^2,24

Patients with acute or worsening chronic ischemia require further assessment and hospital admission or transfer to a center with vascular surgery capability. Patients with chronic peripheral arterial disease without an immediate threat to limb viability absent other acute illness can be discharged home to follow up with a vascular surgeon or primary care physician. Instruct patients to return immediately for worsening of symptoms. Prescribe aspirin (81 milligrams daily after first dose of 325 milligrams) if there are no contraindications.

Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic)² are available at http://circ.ahajournals.org/cgi/reprint/113/11/e463.

UPPER EXTREMITY ISCHEMIA

Acute arterial occlusion in the upper extremities is much less common than in the lower limbs, and due to well-developed collateral circulation around the shoulder and elbow, is better tolerated. Ischemic pain at rest and gangrene, in the absence of distal embolization, are rare in the upper limb. Causes of upper limb ischemia include vasospasm, arteritis, trauma, atherosclerotic plaque rupture, embolism, iatrogenic injury (e.g., during brachial artery access for cardiac catheterization), thoracic outlet syndromes, aneurysms, and hypercoagulable states. After clinical examination, further investigation of suspected ischemia is done with segmental blood pressure measurements above and below the elbow, Doppler evaluation, duplex US, and arteriography. Treatment of acute limb-threatening ischemia of the hand and forearm includes heparin (Table 61-6) and emergent surgical thromboembolectomy.