, Gianmarco de Donato1, Giuseppe Galzerano1, Maria Pia Borrelli1, Giulia Mazzitelli1 and Francesco Setacci2
(1)
Department of Medicine, Surgery and Neuroscience, Unit of Vascular Surgery, University of Siena, Viale Bracci 1, Siena, 53100, Italy
(2)
Department of Surgery “P. Valdoni”, Sapienza University of Rome, Rome, Italy
Keywords
Acute limb ischemiaEmbolismThrombosisDuplex ultrasoundCT angiographyMR angiographyAngiographyIntroduction
Acute limb ischemia (ALI) is a serious medical emergency leading to high rate of complications, being not only limb but even life threatening, often despite early successful revascularization. The prognosis of this potentially devastating disease is mainly related to the rapidity and accuracy of diagnosis and treatment. However, timely recognition of signs and symptoms may be challenging, since clinical onset may range from sub-clinic and pauci-symptomatic to dramatic and irreversible ischemia.
Every specialist involved in the management of vascular diseases (preferably every physician) must be able to promptly recognize the singular signs and symptoms of ALI, avoiding any time loss to the establishment of the correct treatment.
This chapter focuses on epidemiology, natural history, etiology, clinical manifestation, classification, and noninvasive and invasive evaluation.
Definitions, Epidemiology, and Natural History
Acute limb ischemia (ALI) is defined as any sudden decrease in limb perfusion causing a potential threat to limb viability in patients who present within two weeks of the acute event [1]. The incidence of this condition is approximately 15 cases per 100,00 persons per year [2]. The prevalence is <0.1 % in general population and about 5–10 % in patients with other risk factors for cardiovascular disease.
The lower limbs are more frequently involved, being caused by acute arterial thrombosis in the most of cases. The acute ischemia of upper limbs represents only 1/5 of all ALI events, with an incidence of 2.4 cases per 100.000 persons per year. The embolization from a cardiac source is the most common etiology (80 % of cases). Acute upper limb ischemia has a better prognosis quoad vitam and quoad valitudinem than ALI of lower limbs, even if the conservative treatment is associated to a higher risk of limb dysfunction.
Acute lower limb ischemia is still considered to be a dramatic event, carrying a risk of amputation between 15 and 30 % and a high perioperative morbidity and mortality (20–30 %) [3–8]. Concomitant underlying diseases, the metabolic derangement that seems as a result of the acute insult, and a possible reperfusion injury following revascularization may account for this severe prognosis [9–11].
The natural history of any ALI is characterized by the rapid onset of ischemia and by the tissue injuries when the ischemia persists. The sudden cessation of blood supply and nutrients to the metabolically active tissues of the limb, including the skin, muscles, and nerves, is responsible to tissue damage and cell death. Firstly energy metabolism shifts from aerobic to anaerobic process, and then established ischemia leads to cell dysfunction and death.
Nervous tissue cells are the most susceptible to ischemia, followed by muscle cells, the skin, and subcutaneous tissue. Peripheral nerves are perfused by arterioles that anastomosed themselves with a “T shape” along the nerve trunk. The longitudinal vessels that derive from these anastomoses are fundamental for the functionality of the nerve. So lesion of these vessels can lead to serious and irreversible alteration and can explain the failure of nerve resumption even after revascularization. In the pathogenesis of nerve injury, in addition to the ischemia, extrinsic compression due to edematous tissue is important. The prognosis of these lesions is variable: in general, the resumption of sensibility is more common than motility, depending on the time spent between the ischemic insult and revascularization.
Muscle is also sensitive to anoxia due to its high oxygen consumption. Intramuscular edema causes the dissociation of the fibers and the loss of their syncytium feature, instead becomes more evident the transverse streak and starts Bowman degeneration with loss of muscle contractility [12]. The last stage of muscle necrosis is characterized by Zenker’s degeneration in which fibers become swollen and homogeneous and lose their streak. The time of ischemia that a muscle can endure it’s difficult to determine; it seems that within 6 h lesions are still reversible, instead after 12 h they can’t regress [13, 14]. Muscle necrosis can be massive or circumscribed and in the same muscle may coexist different degrees of cell degeneration.
Sequential modifications of the skin are related to the time of ischemia: after 10 h modifications of the nucleus and homogenization of the deep layers are evident, while after 20 h the detachment of basal layers of the papillae occurs. These alterations are still reversible after 48 h. Skin phlyctena, which results from an increased capillary permeability and extravasation of plasma fluid, comes just before gangrene and carries a very high negative prognostic significance.
After ischemia onset, a series of compensatory mechanisms are activated in order to ensure adequate perfusion, including vasodilatation and perfusion through collateral vessels. If these mechanisms are unsatisfactory, secondary thrombosis of distal and smaller vessels may occur.
The rapidity of evolution of any ALI event is related to general and local factors. Systemic hemodynamic conditions are really crucial, since an acute arterial occlusion could be almost completely compensated if systemic blood pressure is satisfactory. On the other hand, extension of thrombosis can occur in case of hypercoagulable concomitant acute episode or real thrombophilic states [15]. Local factors influencing natural history of ALI include the site of occlusion (i.e., more proximal location of clot causes a severe ischemia due to the lower possibility of compensation by the collateral circulation) and a preexisting chronic ischemia, which typically promotes formation of collateral circulation that can ensure distal compensation during an acute event. However, an acute occlusion of these collaterals can determine rapid secondary thrombosis of the whole arterial tree.
Etiology
The etiology of ALI can be roughly distinguished in two large categories: thrombosis and embolism. Distinction of these two conditions is important because treatment and prognosis are different.
Basically any ALI should be distinguished as consequence of embolism or thrombosis [16, 17] and more specifically as occurring on a pathologic or healthy artery or related to other less common conditions (Table 16.1).
Table 16.1
Etiology of acute limb ischemia
1. Embolus |
|---|
Cardiac source |
Atrial fibrillation |
Valvular heart disease |
Endocarditis |
Myocardial infarction (with mural thrombus) |
Atrial myxoma |
Cardiomyopathy |
Arterial source |
Aortic and peripheral arterial aneurysms |
Ulcerated atherosclerotic plaque with intraplaque hemorrhage |
Venous source |
Venous embolism in the presence of inter-atrium or inter-ventricle abnormal communication |
2. Thrombosis |
On pathologic artery |
Atherosclerotic occlusive disease |
Aortic and peripheral arterial aneurysms |
Intraplaque hemorrhage with arterial stenosis and occlusion |
Buerger disease |
Vasculities |
Adventitial cystic disease |
Post-actinic arteritis |
On healthy artery |
Hypercoagulable states (C or S protein deficiencies) |
Entrapment syndromes |
Stasis/low-flow states |
Drugs of abuse |
Heparin-induced thrombosis |
3. Trauma |
Penetrating |
Blunt |
Interventional vascular procedures |
4. Distal progression of aortic dissection |
5. Ischemic thrombophlebitis (phlegmasia cerulea dolens) |
Embolism
The embolic disease is characterized by the presence of a mass (embolus) that travels in the bloodstream and lodges in a blood vessel. The etiology of embolism is changing; before 1950, the majority of ALI (≈60 %) was caused by rheumatic heart disease; today that figure is about 8 %. Nowadays cardiac emboli are commonly associated with atrial fibrillation or mural thrombus after a myocardial infarction. Rarely, the embolus arises from valve vegetation or from an atrial myxoma. Emboli may also arise from aneurysms, so the abdomen and popliteal fossa should be palpated carefully. Atheromatous arteries may also cause distal emboli in case of plaque rupture.
Embolism on Healthy Artery
Embolism on healthy artery may have a cardiac, arterial, and venous origin.
Approximately 80–90 % of all embolisms are associated with heart disease and predisposing conditions as atrial fibrillation, valvular disease, severe cardiac failure, aneurysms of left ventricle, myocardial infarction, thrombus endocarditic vegetation, and valve replacements [18–20]. Clinical onset generally occurs in case of sudden rhythm and frequency modifications, which may occur spontaneously or after drug administration.
Embolism of arterial generally arises from aortic or peripheral (femoral, popliteal) aneurysms but may also be the consequence of atheromatous plaque ulceration or rupture, iatrogenic lesions secondary to invasive diagnostic or interventional procedures, and other lesions of the arterial wall (bruises, compressions, inflammatory processes) [21]. The propulsive element is represented by abrupt modifications of pressure or direct trauma on the artery, especially in the presence of aneurysm.
The circumstance of “paradoxical embolism ” (also called “crossed embolism”) is a rare condition when a venous thromboembolism may reach the arterial circulation through inter-atrium or inter-ventricle abnormal communication, potentially causing arterial ischemia of any tissue.
Other possible causes of embolism on healthy artery include lipid embolism (i.e., trauma, fractures), neoplastic/septic embolism, and air embolism (decompression in divers).
Embolism on Pathologic Artery
In some cases embolism may occur on pathologic artery. This condition is typical of elderly patient with a cardiac source of emboli (i.e., atrial fibrillation) and asymptomatic femoropopliteal artery disease. The embolism causes the acute blood flow blockage at the level of stenotic segment, with consequent thrombosis of collateral vessels causing a severe acute limb ischemia. This kind of embolism should be considered and treated as arterial thrombosis.
Thrombosis
Thrombosis generally occurs in the setting of preexisting vascular lesion. Clinical presentation in case of thrombosis on atherosclerotic stenosis (so-called acute-on-chronic ischemia) may be less severe than in patients with embolic occlusion, as with the former, there may be sufficient collaterals present.
It’s essential to obtain information about any history of claudication or rest pain, to look for the changes associated with chronic ischemia such as atrophy of skin appendages, and to examine the opposite leg for loss of pulses and the presence of bruits.
Thrombosis on Atherosclerotic Plaque
More frequently thrombosis occurs on a pathologic artery for the presence of an atherosclerotic lesion. It is characterized by a referred history of intermittent claudication and cardiovascular disease, and it is generally associated by a less severe limb dysfunction.
Thrombosis of peripheral aneurysm is the second cause of ALI on pathologic artery. The sudden interruption of the blood flow may occur at the level of popliteal aneurysm, but also iliac or femoral aneurysms may occlude acutely. The thrombosis is generally related to an increase of peripheral artery resistances. Emboli can depart from the aneurysmal sac causing an acute occlusion of more distal vessels (blue toe syndrome).
Thrombosis on Non-atheromatous Pathological Artery
This situation may occur in patients with Buerger disease, vasculitis, adventitial cystic disease, and post-actinic arteritis [22, 23]. Thrombosis is the result of the presence of a chronic narrowing in the bloodstream, and clinical presentation is similar to ALI that occurs in patients with atherosclerotic plaques.
Thrombosis on Healthy Artery
Thrombosis may also occur on a healthy artery . This is a less frequent cause of ALI that may be secondary to an ab-estrinseco compression (i.e., popliteal entrapment), to hyperviscosity (hemoconcentration in great dehydrations, thrombophilia, severe hypotension, hemoglobinopathies), to systemic coagulation disorder (congenital anomalies such as protein C or S and antithrombin III deficiencies, malignancy), or to drugs (oestroprogestative, ergotism, drug addiction, chemotherapy). Heparin-induced thrombosis is another important cause of ALI on healthy artery; it is generally recognized by a significant decrease in the platelet count during heparin therapy and the manifestation of the thrombosis.
Extreme low-flow states can produce ALI in patients with hypovolemic shock or cardiac failure, especially when chronic peripheral arterial disease (PAD) is already evident.
Post-traumatic Thrombosis
Trauma may cause acute thrombosis, rupture, or embolism of the artery. Penetrating trauma may directly damage the artery, while blunt trauma may cause indirect injury including spasm, arterial rupture, mural hematoma or intimal dissection, and consequent thrombosis. Blunt trauma may also cause fracture with associated arterial injury.
In case of partial arterial rupture, the natural evolution is represented by pseudoaneurysm formation, vessel occlusion, or artero-venous fistula.
Distal Progression of Aortic Dissection
Occasionally ALI represents the clinical presentation of acute aortic dissection. Patients are typically hypertensive and complain intensive chest and back pain. If aortic dissection is misdiagnosed and patient is treated for ALI by thromboembolectomy , Fogarty catheter passage beyond the occlusion generally fails, carrying the risk of vessel damage and disconnecting part of the dissected intima rather than removing the clot. Of course, failure to determine the correct diagnosis may be fatal.
Ischemic Thrombophlebitis (Phlegmasia Cerulea Dolens)
Infrequent cause of ALI occurs in the setting of massive deep venous thrombosis that causes severe soft tissue swelling of sufficient magnitude to impede arterial inflow to the extremity. Usually, phlegmasia cerulea dolens occurs in those afflicted by a life-threatening illness (underlying malignancy in 50 % of cases).
Clinical Presentation
Clinical Manifestation
When acute limb ischemia occurs, it represents an emergency in which restoration of perfusion through early intervention can lead to limb salvage, whereas delay may results in significant morbidity, including limb loss and, potentially, death. In many ways, this kind of acute vascular disease in the leg may be considered similar to that in the heart. The risk factors, underlying conditions, and pathogenic process are the same, and in many cases, patients have both conditions. And just as cardiologist has learned that in acute myocardial infarction “time is muscle,” the vascular community is coming to recognize that in cases of limb ischemia, “time is tissue.” In fact, as we know, any sudden decrease in limb perfusion—because of either embolic or in situ thrombotic vascular occlusion—can lead a potential threat to limb viability [11, 24].
The rapid onset of limb ischemia results from a sudden cessation of blood supply and nutrients to the metabolically active tissues of the limb, including the skin, muscle, and nerves. The severity of symptoms depends on the level of the obstruction and, most important, the presence of adequate collateral vessels.
The clinical presentation is considered to be acute if it occurs within 2 weeks after symptom onset: symptoms can develop over a period of hours to days. Patients with cardiac embolism, trauma, and aneurysms responsible for peripheral embolization or occlusion of vascular reconstruction tend to present early (hours) due to the severity of symptoms related to the lack of collaterals, the extension of thrombus to arterial outflow, or a combination of both. On the other hand, later presentation—within days—tends to be restricted to those patients with a native thrombosis (“acute-on-chronic ischemia”).
The clinical evaluation of acute limb ischemia should include both a physical examination and an investigation of patient’s medical history: these factors, combined together, could provide clues to the origin of ALI. The collection of medical records should focus on history of claudication, previous ischemic symptoms, and previous vascular reconstruction or diagnostic cardiac catheterization and heart disease. Moreover, any potential risk factor and/or disease contributing to the genesis of the ALI should be carefully investigated (i.e., hypertension, diabetes, smoking, hypercholesterolemia, blood clots, arterial aneurysms as possible embolic sources, family history of cardiovascular disease, hematologic disorders). A correct diagnosis should carefully assess the onset of pain, its abruptness, the location, and the intensity, as well as its change over time and the presence of any motor or sensory deficit. A concomitant examination of the contralateral lower limb provides important suspicions regarding the pre-ischemic status of the involved limb (Table 16.2).
Table 16.2
Clinical features of embolic and thrombotic ALI
Acute embolic occlusion | Thrombotic occlusion | |
|---|---|---|
Symptom onset | Abrupt and severe | More gradual, less severe initially |
Prior PAD | Infrequent | Common |
Contralateral limb | Often normal | Frequent evidence of coexistent PAD |
Coexistent cardiac disease | Frequent (especially AF) | May or may not be present |
ALI typically presents a clinical manifestation of pain, paresthesia, paralysis, pallor, pulselessness, and poikilothermia (so-called six Ps):
The “Six Ps” of ALI Clinical Presentation
Pain
Paresthesia
Paralysis
Pallor
Pulselessness
Poikilothermia
Pain
It is usually severe and progressive, with major localization at most distal part of the extremity. Although pain is generally always present, in diabetic and elderly patients, it may be more vague. The pain of acute ischemia is usually also at the level of the ischemic muscle, which may be tender on palpation or on passive movement of the toes or foot. At the beginning pain is confined and after it became crampy (muscular ischemia). Finally when ischemia continues and sensory deficits appear, they may mask the pain, making diagnosis more complex.
Paresthesia
Nerves are generally very sensitive to ischemia and are rapidly damaged when blood perfusion is interrupted. Fibers responsible for touch impulse are the most sensitive, while pain fibers are less ischemia sensitive. This explains why paresthesia is so frequent in patients with ALI, and it is associated to numbness and tingling in more than half of patients. Because of underlying neuropathy, diabetic patients may already have a sensory deficit that masks the change. When ischemia persists, paresthesia leads to anesthesia.
Paralysis
Motor nerve fibers are more resistant to ischemia. However, when ischemia persists for hours, loss of motor function occurs due to motor nerve fiber injury firstly and because of ischemic injury direct on the muscular issue subsequently. Asking the patient to move and spread the toes generally allows collection of information about the evolution of motor deficit. The degree of motor deficit can vary from mild paresis of toes to complete paralysis of leg, whose prognostic value is really unfavorable. At physical examination muscles injured by ischemia are tender, and this rigid paralysis may simulate consequence of cerebral stroke.
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