INTRODUCTION AND EPIDEMIOLOGY
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.
PATHOPHYSIOLOGY
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.
| Disorder | Cause | Symptoms/Signs | Management |
|---|---|---|---|
| Thrombus | Atherosclerosis or thrombosis of bypass grafts | Intermittent claudication | Medical first, then consider interventional |
| Embolism | Cardiac source: atrial fibrillation, rheumatic heart disease, mechanical valves, post–myocardial infarction thrombus, atrial myxomas and leaflet vegetations | Sudden onset of territorial arterial symptoms | Preventative anticoagulation, embolectomy |
| Catheterization complication (brachial or femoral) | Can occur during standard angioplasty, angiography, or arterial blood gas | Expanding hematoma, pain, temperature and pulse changes | Conservative vs. operative repair |
| Trash foot or blue toe syndrome | Cholesterol/platelet aggregate emboli | Painful cyanotic discoloration of isolated portion of foot; remainder of the foot is warm | Conservative therapy |
| Vasculitis: rheumatoid arthritis, lupus, polyarteritis nodosa | Autoimmune inflammation of small arteries | Systemic symptoms and multiorgan ischemia | Steroids, immunosuppressive agents |
| Raynaud’s disease | Vasospasm in small arteries or arterioles provoked by cold or stressors | Local pain, pallor, cyanosis, numbness, paresthesias in hands usually resolving in 30–60 min | Rewarming, medications: calcium channel blockers, α-blockers, vasodilators |
| Takayasu’s arteritis | Autoimmune vasculitis of aortic arch and branches | Young Asian women: peripheral ischemia and necrosis leading to pulseless phase; may have fever, rash, muscle aches, arthritis | Steroids, immunosuppressive agents |
| Thromboangiitis obliterans (Buerger’s disease) | Nonatherosclerotic segmental inflammation of small/medium vessels; typically, only seen in smokers | Painful nodules, ulceration, and gangrenous digits in young adults (age 20–40 y) | Smoking cessation |
| HIV arteritis9 | Chronic inflammation of arteries associated with low CD4 counts | Intermittent claudication | Optimization of HIV management, angioplasty, or vein graft |
| Hypothenar hammer syndrome | Repeated trauma to the hypothenar area with hammering in laborers, as well as those using vibrational tools, causing narrowing of ulnar artery or aneurysmal degeneration | Painful discoloration of one or more ulnar fingers with sparing of thumb | Aspirin, nifedipine, intra-arterial fibrinolysis, interposition vein graft |
| Popliteal artery entrapment (young males) and popliteal aneurysms (older males)10 | Anatomic crowding of popliteal fossa with anomalous relationships between popliteal artery and surrounding muscle and fascia or luminal narrowing and thrombosis of aneurysm | Pain in anterior aspect of lower one third of leg with exercise, reproducible with active ankle plantar flexion or passive dorsiflexion | Surgical repair of popliteal fossa or aneurysm and grafting |
| External iliac artery endofibrosis11 | External iliac artery fibrosis secondary to prolonged hip flexion | Thigh pain and numbness in cyclists and triathletes: measure pre- and postcycling ankle-brachial indexes | Surgical management or catheter dilatation |
| Local arterial trauma12,13 | Penetrating or blunt damage to vessel | Suspect in patients with knee dislocation or penetrating extremity trauma | Surgical repair |
| Shock-related arterial ischemia | Low cardiac output states: congestive heart failure, sepsis, cardiogenic or hypovolemic shock | Generalized hypoperfusion | Resuscitation with fluids, blood products, vasopressors, inotropes; treat infection |
| Thoracic aortic dissection | False lumen of dissection occludes arteries | Chest or back pain | Surgical repair |
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.
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.
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.
CLINICAL FEATURES
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.
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