Embolism to the lower extremities

INTRODUCTION — Embolism to the lower extremities is caused by material that has traveled from elsewhere in the body (table 1). The material that has lodged in the extremity decreases blood flow because of occlusion or severe stenosis of the blood vessel. By understanding the breadth of that definition, the variables of "material" and "elsewhere in the body" provide a way to systematically think through the various etiologies. In addition, a systematic approach helps to avoid jumping to diagnostic conclusions based purely on what is common or clinically familiar.

The priorities of managing acute embolism to the lower extremities are first to address the ischemia and then to institute measures to prevent further embolic events.

The clinical presentations, evaluation, diagnosis, and general management of embolism to the lower extremities are reviewed here. Other causes of acute arterial occlusion to the lower extremities are reviewed elsewhere. (See "Clinical features and diagnosis of acute lower extremity ischemia".)

ETIOLOGY — Etiologies leading to lower embolism are shown in the table and discussed below (table 1).

Cardiac sources — The most commonly reported source of lower extremity emboli is the heart, accounting for 55 to 87 percent of events [1-3]. The main sources of embolism from the heart are thrombus from within the cardiac chambers and debris shedding off valves (native, prosthetic). Rarely, cardiac tumor (eg, atrial myxoma) can also embolize [4].

Emboli from intracardiac thrombus usually come from the left atrium, often associated with atrial fibrillation. Thrombus can also form in the left ventricle (eg, severe cardiomyopathy, post-myocardial infarction). In either case, an area of relative stasis within the heart allows thrombus to form locally, which can dislodge and embolize to virtually anywhere in the body, including the lower extremities. Intracardiac sources of thrombus are often fibrin rich, with acute thrombus generally responding well to thrombolytic agents (eg, tissue plasminogen activator) [5]. (See "Left ventricular thrombus after acute myocardial infarction" and "Atrial fibrillation in adults: Selection of candidates for anticoagulation".)

The aortic or mitral valves can also be sources of emboli to the lower extremities. This may be from debris on diseased native or prosthetic valves, vegetative growths from bacterial endocarditis, or nonbacterial vegetations such as Libman-Sacks endocarditis in lupus [6,7]. As these types of embolic debris are not largely thrombotic in nature, they do not respond well to thrombolysis. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis" and "Prosthetic valve endocarditis: Epidemiology, clinical manifestations, and diagnosis".)

When septic emboli from cardiac valves lodge in the lower extremity, they can cause local destruction of the artery, abscess formation, and/or mycotic pseudoaneurysms in addition to the usual ischemic picture. (See "Complications and outcome of infective endocarditis", section on 'Septic embolization' and "Overview of infected (mycotic) arterial aneurysm".)

Aortic plaque — A diseased aortic wall with complex atherosclerotic plaque can also be a source of emboli. Presumably following the rupture of the fibrous cap overlying an atherosclerotic plaque, luminal irregularities and ulcerations result in a surface that is thrombogenic [8]. In addition to embolization of larger pieces of accumulated thrombus, microembolization of cholesterol crystals can also occur. (See "Thromboembolism from aortic plaque" and "Embolism from atherosclerotic plaque: Atheroembolism (cholesterol crystal embolism)".)

Asymptomatic atherosclerotic disease of the aorta often seen incidentally on imaging studies (the so-called "shaggy aorta syndrome") can lead to macrovascular or microvascular embolization (or both) [9,10]. This can occur anywhere along the aorta, including the ascending aorta, aortic arch, descending thoracic aorta, or abdominal aorta.

Another source of emboli from the aorta is thrombus that appears to be nearly free-floating with attachment at one end to the wall of the aorta (also known as mural thrombus, mobile aortic thrombus, pedunculated aortic thrombus) [11]. Sometimes these are found incidentally on imaging studies and other times during the evaluation for an embolic source. When surgically removed, the attachment point appears often to originate from an intimal irregularity/defect, suggesting that these may start from a ruptured plaque or other primary intimal defect.

Aortic and peripheral aneurysm — Blood flow within aortic aneurysms (thoracic or abdominal) is altered such that mural thrombus frequently forms within the aneurysm sac. Unlike with rupture risk, there is no known association of embolic potential of aortic aneurysms relative to their diameter. Although mural thrombus in an aortic aneurysm is common, dislodgement of aortic thrombus is an uncommon but known source of embolization to the lower extremities [12]. Embolism may be spontaneous, during manipulation of the aneurysm during open or endovascular repair, or during arterial instrumentation for another reason. (See 'Instrumentation' below.)

Although iliac artery aneurysms are more likely to be complicated by rupture, thrombosis with the potential for embolism can occur.

Peripheral aneurysms such as femoral and popliteal aneurysms have a propensity to thrombose, which may propagate to occlude the distal vasculature, or alternatively, mural thrombus can embolize distally. (See "Femoral artery aneurysm" and "Popliteal artery aneurysm".)

Paradoxical embolism — A paradoxical embolus results from venous thrombus embolizing to the right heart and then crossing into the arterial circulation through an intracardiac septal defect, or a right-to-left shunt in the pulmonary circulation.

Although the most commonly described manifestation of paradoxical embolism is acute stroke, embolization elsewhere in the peripheral arterial system has been described, including to the lower extremities. Because these clots originate in the veins, they tend to be larger, and when they embolize to the lower extremities, they tend to obstruct larger vessels.

A timely diagnosis of paradoxical embolism requires a high index of suspicion because of the low prevalence of structural defects (eg, patent foramen ovale, atrial septal defect) that allow crossing from the venous to arterial circulation.

Instrumentation — The incidence of lower extremity embolization as result of cardiac or peripheral interventions (catheter based or surgical) is quite low, but it is important to consider as a potential etiology when evaluating an embolic event. (See "Complications of diagnostic cardiac catheterization", section on 'Atheroembolism' and "Access-related complications of percutaneous access for diagnostic or interventional procedures", section on 'Atheroembolism' and "Access-related complications of percutaneous access for diagnostic or interventional procedures".)

Endovascular intervention — Careful manipulation of wires, catheters, and treatment devices during endovascular interventions is important to minimize damage from the intervention itself. Disruption of plaque or thrombus can occur during any type of intervention, including diagnostic studies and stent or stent-graft placement. (See "Endovascular techniques for lower extremity revascularization", section on 'Complications and management' and "Access-related complications of percutaneous access for diagnostic or interventional procedures".)

The incidence of iatrogenic embolization is not well known, but angiographically or clinically noted macroembolic events are estimated to occur in 2 to 5 percent, with smaller, undetected microembolic events likely occurring at much higher rates [13,14]. The clinical implications of microembolic events are not well known [15].

The intraprocedural embolic event may be recognized at the time of the procedure on completion imaging that shows a new filling defect or loss of outflow vessels. Early recognition provides an opportunity to immediately address the problem, with the goal of minimizing negative clinical effects, which can often be accomplished using endovascular means. Embolization related to instrumentation can also occur in a delayed manner after the intervention has been completed.

Arterial closure devices — A variety of arterial closure devices (suture-mediated closure, metal clip-mediated closure, collagen or other soluble plugs) can be used at the end of endovascular procedures, usually with good results [16]. Vessel thrombosis and/or distal embolization are potential complications of these devices, with embolization occurring infrequently (<1 percent) [17-19].

Such complications are usually related to an unrecognized maldeployment of the device such that an external component is deployed within the vessel wall or intraluminally. Although the component may be designed to dissolve over time, the timeframe is usually over weeks to months. Any narrowing of the vessel causing ischemia will usually need to be addressed sooner.

CLINICAL PRESENTATIONS — The clinical presentation of lower extremity embolization varies depending upon the source of the thrombus, the size of the embolic debris, and the ability of the extremity to compensate for reduced flow related to the obstruction, which varies by the location of the obstruction. Some clinical presentations increase suspicion for certain etiologies.

Emboli tend to lodge at arterial branch points where the caliber of vessels changes or at a site of narrowing from a preexisting atherosclerotic plaque. In one of the largest series on embolic disease, lower extremity emboli accounted for 63 percent of events, with the femoral artery affected most commonly (28 percent), followed by the aortoiliac segment (18 percent), and then the popliteal segment (17 percent) [20].

Acute limb ischemia — The working definition of acute limb ischemia is based on the 2007 Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II), which describes acute limb ischemia as "a quickly developing or sudden decrease in limb perfusion, usually producing new or worsening symptoms or signs, and often threatening limb viability" [21]. The duration of symptoms that distinguishes acute from chronic limb ischemia is defined as <2 weeks [22-24].

Emboli from cardiac sources or paradoxical emboli tend to lodge in larger arteries and tend to occur in individuals even without peripheral artery disease. Symptoms are sudden and rapidly progressive. The severity of the initial presentation corresponds to the degree of urgency needed for treatment [22].

Blue toe syndrome — Digital ischemia with intact large vessel circulation, also called the "blue toe" syndrome, is a variation of acute limb ischemia, except that the size of the embolic material is small enough to travel into the end arteries [25,26]. (See "Embolism from atherosclerotic plaque: Atheroembolism (cholesterol crystal embolism)", section on 'Blue toe syndrome'.)

The patient will often have intact pedal pulses, but there is inadequate circulation to the individual toe(s). In patients who do not have concomitant neuropathy or other sensory deficits, this condition is extremely painful. The toe will often become discolored, hence this syndrome's moniker. The clinical course after the acute insult varies, sometimes with complete resolution, other times with chronic pain/nerve damage but with preservation of the toe, and at other times with progression to gangrene and need for toe amputation. Unless extensive, there is minimal threat of major (above-ankle) amputation.

Subclinical progression to chronic ischemia — In contrast to acute limb ischemia, repeated emboli to the lower extremities can manifest with a stepwise deterioration of distal arterial flow from individual embolic events that have either no or mild symptoms.

Disruption of the lower extremity outflow circulation can become sufficiently severe to cause rest pain or tissue loss. The resultant clinical presentation is similar to chronic peripheral artery disease but with an embolic rather than atherosclerotic or other etiology [27,28]. (See "Clinical features and diagnosis of lower extremity peripheral artery disease".)

Subclinical progression can appear clinically and is angiographically similar to other common pathologies that predominantly affect the tibial vessels, such as patterns of peripheral artery disease in patients with diabetes or renal failure, Buerger's disease, vasculitis, or repetitive arterial trauma.

Subclinical progression can be difficult to treat because the reduced arterial outflow limits the available treatment options and durability of treatment.

CLINICAL EVALUATION — The clinical evaluation identifies the nature of the clinical presentation, grades the severity of ischemia, and considers the potential sources of embolization, all of which are used to determine the appropriate course of treatment and to institute treatment to prevent future embolic events. A systematic approach is used to avoid missing potential embolic sources that can lead to recurrent embolism. The extent and timing of the clinical evaluation largely depends on the nature of the clinical presentation. (See 'Clinical presentations' above.)

●For acute limb ischemia, management of the limb takes priority over determining the source of the embolus. The evaluation focuses primarily on what is necessary to make appropriate treatment decisions, namely determining clinical severity, defining the anatomy, and identifying comorbidities that may influence treatment. Identifying the suspected embolic source may need to be deferred until after treatment is begun.

●For other presentations (eg, subclinical progression, blue toe syndrome), acute treatment options may be limited, and the emphasis is on preventing future embolic events.

History and physical — The history should evaluate risk factors associated with lower extremity embolism. (See 'Etiology' above.)

●A history of atrial fibrillation, valve replacement, structural heart defects, or known valvular problems may point toward a potential cardiac source, but it must be kept in mind that for some people, cardiac disease may be undiagnosed.

●For patients who are anticoagulated, it is important to identify the reason for anticoagulation and whether the medication is being taken regularly and as prescribed, as well as when the last dose was taken. For patients taking warfarin for atrial fibrillation, a nontherapeutic international normalized ratio (INR) increases the risk for embolization. In a Veterans Administration study of over 34,000 patients with nonvalvular atrial fibrillation, low INR (<2.0) increased the risk for systemic embolization (relative risk 6.3; 95% CI 4.4-8.9) [29].

●Coexisting peripheral artery disease (PAD) may alter the manner in which an embolic event presents. It is important to determine the baseline symptoms, which may help determine the acuity of the current symptoms and, after treatment, whether there has been a return to baseline. For patients with diabetes and PAD, a history of any baseline neurologic deficits is important.

●For the patient with a known history of aneurysmal disease or a family history of aneurysms, it is important to consider all potential aneurysm sites. Aneurysm in one location increases the risk for aneurysms in other locations. Patients with an abdominal aortic aneurysm have a prevalence of approximately 20 percent for popliteal aneurysms, many of which may not be easily detected on physical exam [30]. Up to 80 percent of patients with one peripheral aneurysm have multiple aneurysms, and in patients with a popliteal aneurysm, the incidences of aortoiliac and bilateral popliteal aneurysms are approximately 60 and 50 percent, respectively [31].

●The patient should also be asked about any recent catheterization procedures.

A thorough examination evaluates for signs of acute limb ischemia (six Ps) and any signs of chronic limb ischemia. For the lower extremity, this involves evaluating the femoral, popliteal, dorsalis pedis, and posterior tibial pulses bilaterally. (See "Clinical features and diagnosis of acute lower extremity ischemia", section on 'Six Ps' and "Embolism from atherosclerotic plaque: Atheroembolism (cholesterol crystal embolism)", section on 'Clinical manifestations' and "Clinical features and diagnosis of lower extremity peripheral artery disease", section on 'Physical examination'.)

Often in acute presentations, the history and physical examination may be all that is necessary to guide therapy. As an example, an absent femoral pulse in the affected extremity but a normal or near-normal pulse examination in the unaffected extremity in a patient with an appropriate history (eg, atrial fibrillation) may be all that is needed to proceed to embolectomy. (See 'Approach to limb management' below.)

Classification of ischemia — Based on the clinical findings, the severity of acute ischemia should be classified (table 2), which is important for guiding further evaluation and management [22,32]. (See "Classification of acute and chronic lower extremity ischemia", section on 'Acute extremity ischemia' and "Classification of acute and chronic lower extremity ischemia", section on 'Chronic extremity ischemia' and 'Approach to limb management' below.)

Laboratory studies — Laboratory information is obtained initially to assess treatment risks and to serve as a baseline for subsequent comparison. The patient will at least be started on anticoagulation and has a high likelihood of being administered iodinated contrast for catheter-based arteriography or computed tomographic (CT) angiography at some point during diagnosis and treatment. As such, we obtain a complete blood count, basic metabolic panel, prothrombin time/international normalized ratio (PT/INR), and partial thromboplastin time (PTT). For patients in whom thrombolysis will be considered, a baseline fibrinogen level should be included with the coagulation profile. If there is a suspicion of malnutrition or liver disease, we often gather a complete metabolic panel as a baseline. Identifying problems early can identify those at higher risk for surgical complications and guide appropriate postoperative and discharge management.

Vascular imaging — Whether or not to proceed with vascular imaging depends upon the suspected cause, physical findings, and the severity of ischemia. For patients with acute lower extremity embolism, the history and physical examination may be sufficient to provide the diagnosis and to initiate treatment. Whenever feasible, we suggest obtaining CT angiography because it provides valuable information about the location of embolic debris (image 1) and the amount and location of baseline atherosclerotic plaque burden, and it will detect aneurysmal disease. Even in the setting of acute limb ischemia, CT angiography can usually be quickly accomplished while preparing the patient for intervention. The information gained from CT angiography may also be helpful for deciding whether to pursue open surgery or catheter-based intervention as well as aiding with the specifics of the chosen approach. As an example, if an open approach would be favored, then arterial puncture for angiography, which comes with its own risks, can be avoided. The benefits of CT angiography must be weighed against any potential risks (eg, treatment delays, worsening renal function).

The objective is to obtain good imaging of the lower extremity vasculature as well as the abdominal and pelvic inflow. Although complete vascular imaging would be desirable, it is often very difficult to get good-quality images of the chest, abdomen, pelvis, and bilateral lower extremities with a single contrast bolus. In this setting, evaluation of the chest can be deferred until the postoperative period, if still needed. (See 'Subsequent diagnostic evaluation' below.)

Magnetic resonance (MR) angiography has limitations when evaluating acute embolic disease, one of which is the additional time needed to complete the study. The extent of calcium within the walls of the vessels is particularly relevant for deciding the best way to obtain proximal and distal control of the artery during open surgery. Calcium is poorly visualized, and the spatial resolution may also be limited for evaluating ulcerative plaques or irregular atheroma, but this can vary by available equipment and protocols. (See "Advanced vascular imaging for lower extremity peripheral artery disease".)

INITIAL MANAGEMENT — Initial management of acute embolism to the lower extremities includes systemic anticoagulation and intravenous fluid therapy, which can be started while awaiting evaluation by a specialist trained to treat the lower extremity embolic event (typically a vascular surgeon). Medical risk assessment, which may require consultation with medicine or cardiology services, should also be initiated to aid in selecting the best option for treatment.

Anticoagulation — Systemic anticoagulation should be initiated as soon as the diagnosis of embolism is made on clinical grounds, and before subsequent imaging [21,23,33]. Typically, systemic anticoagulation consists of intravenous unfractionated heparin using a weight-based protocol to administer a bolus (60 to 80 units/kg) followed by an initial infusion of 12 to 18 units/kg/hour, titrated to maintain the anticoagulation target. An alternative agent may be used in those with contraindications to heparin. Patients should remain anticoagulated and monitored for progression of ischemia throughout any vascular imaging. (See "Heparin and LMW heparin: Dosing and adverse effects", section on 'Dosing and monitoring' and "Management of heparin-induced thrombocytopenia (HIT) during cardiac or vascular surgery".)

Anticoagulation prevents further propagation of thrombus and inhibits thrombosis distally in the arterial and venous systems due to low flow and stasis. Anticoagulation may result in clinical improvements that may decrease the threat to the limb as collaterals open up and vasospasm improves, possibly allowing more time for evaluation and treatment.

If anticoagulation is discontinued temporarily for any reason, it should resumed as soon as feasible postoperatively based on the bleeding risk profile of the intervention. We often find that a heparin drip can be resumed within the first few hours postoperatively, and then the patient is monitored for bleeding complications before transitioning to an oral anticoagulant. For some patients, systemic anticoagulation alone may serve as definitive treatment [34]. This strategy may be useful for very-high-risk patients with viable limbs and some with marginally threatened limbs who have numerous comorbidities or more pressing medical issues. (See 'Medical therapies' below.)

Medical risk assessment — The majority of patients with lower extremity embolism have underlying cardiovascular disease. The severity of any underlying cardiac condition(s) may increase the risk of treatment and limit the options available for restoring blood flow to the ischemic extremity. When time allows, preoperative cardiac evaluation should be included in the management of these patients to assess surgical risk. (See "Evaluation of cardiac risk prior to noncardiac surgery" and "Management of cardiac risk for noncardiac surgery".)

For patients who require emergency revascularization, a baseline electrocardiogram, chest radiography, and a clinical history of the patient's level of activity (ie, whether or not the patient can perform >4 metabolic equivalents) help stratify risk. An echocardiogram can usually be obtained following revascularization; however, if thrombolytic therapy is being considered, obtaining an echocardiogram beforehand is useful to evaluate for mural thrombus.

APPROACH TO LIMB MANAGEMENT — While embolism to the lower extremities has a variety of potential causes as well as treatment strategies, the approach to limb management strongly depends on the clinical presentation, particularly the severity of limb ischemia at presentation (table 2) and duration of symptoms [23]. (See 'Classification of ischemia' above.)

Other factors that may play into decision making include the etiology and anatomy of the embolic occlusion, runoff quality below the occlusion, patient comorbidities, prior operations, endovascular device availability, and contingency plans in the event of treatment failure [35].

By severity of acute ischemia

Viable or marginally threatened extremity — For most patients with a viable or marginally threatened extremity, based upon the outcomes of several randomized trials, we agree with major society guidelines that support an initial attempt at thrombolysis for appropriately selected patients [23,33,36-38]. For viable limbs, treatment can usually be approached urgently rather than as an emergency.

Clinical features that are useful for determining whether thrombolysis or surgical revascularization is the most appropriate initial treatment include the following:

●Presumed etiology

●Lesion location and length

●Duration of symptoms

●Suitability of the patient for surgery

●Availability of autologous vein for bypass grafting

As examples, proximal thrombus (eg, aortoiliac, common femoral artery) may be more amenable to thrombectomy. On the other hand, an embolus to a distal vessel (eg, tibial artery) may be best treated with thrombolysis. In general, older thrombus (eg, from aneurysm sac) does not respond well to thrombolysis, and thrombolysis has no effect on nonthrombotic material, so if either is strongly suspected, surgery may be the preferred treatment. In patients who have previously undergone surgery, reoperative fields can make surgical exposure more difficult, increasing the risk for complications. In addition, peripheral artery disease can make an embolectomy more challenging. High-grade stenoses can make it difficult to pass embolectomy catheters, and calcified plaque tends to pop the embolectomy balloon. Arterial dissection can also occur from the catheter passing behind the plaque. Passing an embolectomy through a recent stent or vascular anastomosis increases the risk of dislodging the stent or rupturing the vessel. However, in such complicated instances, an endovascular-first strategy with catheter-based thrombectomy may allow for treatment of the acute change with the addition of other endovascular adjuncts as needed.

Thrombolysis is generally a safe and effective alternative to surgery for appropriately selected patients [39,40]. However, failure of thrombolysis can lead to progression of ischemia to a higher degree of limb threat that may necessitate conversion to immediate surgical revascularization to reduce the risk of limb loss. Although the success of thrombolytic therapy may be limited by the time required to dissolve thrombus and severity and duration of ischemia, when subsequent revascularization is needed, the magnitude and complexity of the procedure is frequently less for those receiving compared with not receiving prior thrombolytic therapy. (See 'By etiology/anatomy' below and 'Intra-arterial thrombolysis' below and 'Open embolectomy' below.)

Immediately threatened extremity — For most patients with an immediately threatened extremity, surgical revascularization is the most appropriate initial treatment. (See 'Open embolectomy' below.)

Patients with an immediately threatened limb are generally not good candidates for thrombolysis. Although pharmacologic thrombolysis may successfully dissolve the embolus, the time required is usually too long for it to be an acceptable alternative to surgery. Progression to an unsalvageable limb can occur in as little as four to six hours if prompt revascularization is not performed. Thus, open embolectomy is preferred; however, some clinicians may initiate thrombolysis in selected clinical circumstances, such as if the neurologic deficits are mild and open revascularization represents an excessive risk for the patient. If thrombolysis is to be considered at all, the limb needs be closely monitored to identify any signs of deterioration, which can happen quickly. In addition, there needs to be expedient operating room availability in the event of clinical worsening to convert emergently to open surgical revascularization for appropriate candidates.

With technical advancements and greater availability of catheter-based thrombectomy systems, we often will start with this approach for more distal embolizations as we can remove thrombus expeditiously and potentially treat the source at the same setting in selected cases of dissection, ulcerated plaque, or aneurysm. Thrombolysis can be added if needed, and by removing some of the occlusive material the improvement in flow may be sufficient to provide more time for thrombolysis to be effective. In addition, percutaneous thrombectomy can provide an image-guided thrombectomy while avoiding reoperative surgery, which is associated with higher rates of dehiscence and surgical site infection. In addition, for those with prosthetic graft, avoiding graft exposure helps reduce the risk of prosthetic graft infection.

Depending upon the duration and severity of the ischemia, a fasciotomy may be required to prevent the development of compartment syndrome following reperfusion. (See "Acute compartment syndrome of the extremities" and "Lower extremity fasciotomy techniques".)

Nonviable extremity — Patients with nonviable extremities should undergo prompt amputation. Vascular imaging prior to surgery is usually not necessary since the level of amputation is determined by clinical findings and by the viability of tissues at the time of surgery. Every effort should be made to preserve as many joints as possible to decrease the work of ambulating with a prosthetic, which improves the likelihood for successful rehabilitation. Delays in amputation of a nonviable extremity can result in infection, myoglobinuria, acute renal failure, and hyperkalemia. However, if these risks can be monitored, we often provide a couple days of therapeutic anticoagulation as long as the patient is not developing any of these issues. By anticoagulating and allowing for collateral flow to develop, a longer residual limb may result which improves postamputation function. (See "Lower extremity amputation" and "Techniques for lower extremity amputation".)

By etiology/anatomy

●Suspected cardiac source – Emboli from cardiac sources tend to be large and lodge at the bifurcations of major lower extremity vessels, such as the aortic bifurcation or common femoral artery. These patients often do not have underlying atherosclerotic vascular disease, present without a femoral pulse on the affected side, and have a normal vascular exam on the contralateral side. These clinical features may be all that is needed prior to taking the patient to the operating room. In this setting, open embolectomy is generally the best procedure, given that these emboli are often are too large to aspirate and may have limited response to thrombolysis, though exceptions may exist.

Echocardiography for evaluating cardiac embolic sources is generally deferred to prevent any delays in revascularization. For facilities with the means to obtain echocardiography without causing a delay in revascularization, or ability to perform the study intraoperatively, echocardiography prior to or in conjunction with revascularization may be reasonable. (See "Echocardiography in detection of cardiac and aortic sources of systemic embolism".)

●Distal vessel occlusion/thrombosis – For patients who have little to no flow in the distal vessels on initial arteriography, we suggest thrombolysis to improve outflow, which may be combined with transcatheter embolectomy to reduce, and for some patients, eliminate the need for thrombolysis. Occlusion of the distal vessels can be the direct result of embolization or can be due to low flow from a more proximally lodged embolus. The outflow may thrombose to the extent that no suitable target is available for revascularization on initial arteriography. Clearing distal thrombus may reveal treatment options for subsequent open and/or endovascular treatment that were not apparent on initial arteriography.

For patients whose history suggests that the embolic material is chronic thrombus (eg, mural thrombus from aneurysm, aortic thrombus) or nonthrombotic material (eg, tumor, embolized device fragments), open embolectomy or transcatheter embolectomy are better options compared with thrombolysis as these materials are not likely to or simply will not respond to thrombolytic agents.

For patients with recurrent embolism leading to subclinical progression, the suspected embolic source needs to be found and treated. Revascularization is performed as needed based upon clinical symptoms and anatomy, similar to the approach for chronic peripheral artery disease. (See "Management of chronic limb-threatening ischemia".)

●Embolization during intervention – When distal embolization occurs during a peripheral intervention, it is ideally identified at the index procedure and treated in the same setting. This can often be done by aspirating the embolic material through a catheter (ideally a percutaneous thrombectomy catheter system, though a guiding catheter can sometimes be successful). Sometimes, applying low doses of tissue plasminogen activator (tPA; 2 to 4 mg) through the catheter into the affected vessel can dissolve the embolized material, particularly when embolus is very distal. Rarely, in larger vessels it may be necessary to place a stent to trap the embolized material against the vessel wall to preserve luminal flow [41]. (See 'Percutaneous embolectomy' below and 'Intra-arterial thrombolysis' below.)

●Blue toe syndrome – The treatment of blue toe syndrome is predominantly medical, so it is important to recognize it when it occurs; otherwise, the patient could be subjected to treatments that are ineffective. (See "Embolism from atherosclerotic plaque: Atheroembolism (cholesterol crystal embolism)", section on 'Treatment'.)

TECHNIQUES

Intra-arterial thrombolysis — Intra-arterial thrombolysis involves placing a catheter percutaneously to administer a thrombolytic agent directly (eg, tissue plasminogen activator [tPA]) into an artery to break down thrombus. Pharmacomechanical thrombolysis involves the additional use of mechanical force to assist in breaking up the clot. The mechanism differs among the various devices [42,43]. Some devices can also be used as a mechanical thrombectomy device alone if there are contraindications to thrombolysis. (See "Intra-arterial thrombolytic therapy for the management of acute limb ischemia".)

Prior to initiating thrombolysis, patients should be screened for contraindications to thrombolytic therapy (table 3) [37]. Severe complications of thrombolysis include intracranial hemorrhage, which has high mortality, and major gastrointestinal bleeding, which is potentially life-threatening.

Thrombolytic therapy can be initiated in a hybrid operating room suite, a standard operating room with portable C-arm capabilities, or an interventional suite. Whenever thrombolysis is performed, it is important to have an operating room available in the event that ischemia progresses during thrombolysis, the treatment fails, or bleeding occurs that requires operative intervention.

Open embolectomy — One of the main advantages of open embolectomy is that blood flow is generally restored quite quickly. However, revascularization may be accompanied by adverse cardiac events due to sudden release of acid and potassium from the tissue in cases of advanced ischemia.

For patients with large emboli that lodge at/near the femoral bifurcation, an open embolectomy is an expedient solution that can be performed on almost any patient. If comorbidities increase the risk for general anesthesia, a femoral cutdown and embolectomy can be performed under regional or local anesthesia.

Either a transverse or longitudinal incision can be made over the common femoral artery. If the vessel is soft and healthy, a transverse arteriotomy is made for embolectomy, which prevents luminal narrowing on primary repair. If the artery is diseased, we generally prefer to use the longitudinal incision because it provides greater flexibility for additional exposure if a concomitant endarterectomy and patch angioplasty becomes necessary.

From the single arteriotomy, Fogarty balloon catheters can be passed proximally into the iliac artery and distally into the superficial and deep femoral arteries, and often down to the popliteal artery. A #5 Fogarty is often sufficient for the common femoral and iliac arteries, and a #4 Fogarty is typically used in the superficial femoral artery, although smaller or larger catheters may be necessary as the circumstances dictate. To embolectomize down to the popliteal artery from the groin, a #3 Fogarty catheter will often be necessary. Once strong inflow and backbleeding are obtained with clean passes of the Fogarty embolectomy catheters, intraoperative completion arteriography is performed to evaluate the adequacy of distal blood flow. Intraoperative administration of a thrombolytic agent directly into the distal vessels may be necessary if small emboli are still present in the runoff vessels.

If needed, additional exposures of the below-knee popliteal artery at the tibial trifurcation and/or distal tibial/pedal vessels can be used to ensure adequate flow. Passing embolectomy catheters into tibial vessels requires extreme care as these vessels are easily injured. A #2 Fogarty is generally used for tibial vessels. Very distal thrombus can sometimes be treated with localized intra-arterial tPA injection. Spasm of otherwise healthy vessels or dissection of the arteries can occur with embolectomy. If spasm is suspected, intra-arterial administration of a vasodilator such as nitroglycerin or papaverine will often resolve the issue. If a dissection is flow limiting, angioplasty and/or stenting may be required.

If embolectomy fails, bypass grafting may become necessary, although for purely embolic events without baseline peripheral artery disease, this is rarely necessary. For immediately threatened limbs, prosthetic graft (ie, polytetrafluoroethylene [PTFE]) is often chosen to avoid the time needed for vein harvest, which expedites restoration of blood flow with the tradeoff of decreased expected patency. Individual surgeons need to weigh the risks and benefits for each patient based on the clinical scenario. (See "Lower extremity surgical bypass techniques".)

Percutaneous embolectomy — Techniques for percutaneous, catheter-based thrombus extraction have been developed that use percutaneous thrombectomy catheter systems, guiding catheters or other devices to engage thrombus and directly aspirate embolus. These are particularly useful for cases of intraprocedural embolization of plaque/thrombus large enough to lodge in major runoff vessels or in cases where there is a contraindication to the use of thrombolytic agents. One such device, which is based off the same platform that has been used for neuro-rescue in acute strokes, is also available in catheter sizes and lengths for treating lower extremity emboli, even those occurring distally [44]. Comparative studies in patients with embolization or acute ischemia are limited; however, data from acute ischemic stroke treatment suggest some benefit compared with thrombolysis [45].

While sometimes used in isolation, transcatheter embolectomy is often combined with other established endovascular therapies such as thrombolysis or angioplasty/stenting. Alone or combined with other techniques, it appears to be safe and effective in appropriately selected patients [46,47]. Compared with open bypass, transcatheter embolectomy with or without adjunctive treatments likely has lower amputation-free survival in cases of acute limb ischemia affecting below-knee vessels as well as in diseased native vessel occlusion similar with other interventions [48]. This is most likely related to the complexity of the presenting disease process rather than a specific failure of the technology, given that open embolectomy also has better outcomes in vessels above compared with below the knee. A Cochrane review has highlighted the need for higher quality studies to make recommendations regarding treatment with endovascular technologies [49]. More robust comparative studies and longer follow-up data will be needed, but this technology represents a potential area of innovation for embolism treatment.

PREVENTING FUTURE EMBOLIC EVENTS — After managing the acute ischemic insult, further evaluation and treatment focuses on preventing recurrent embolic events. Once the acute limb issues have been attended to, the subsequent diagnostic evaluation is focused on identifying the suspected embolic source. Once the source is known, treatment may involve additional intervention to remove or exclude the source from the circulation or use of adjunctive medical therapies.

Subsequent diagnostic evaluation

Echocardiography — Echocardiography is an integral part of the subsequent evaluation to determine the source of the embolus. Obtaining this study can generally be performed after the intervention for acute ischemia and should not delay treatment.

Echocardiography can detect the presence of residual thrombus in the left atrium as well as evaluate for possible valvular pathology. If valvular vegetations are strongly suspected, a transesophageal echocardiogram (TEE) may be required given better sensitivity and specificity. (See "Transesophageal echocardiography in the evaluation of the left ventricle" and "Echocardiographic evaluation of the atria and appendages".)

TEE can also identify thoracic aneurysmal disease and aortic plaque and can provide dynamic visualization of mobile aortic thrombus or plaque that could be the source of distal embolization. (See "Thromboembolism from aortic plaque", section on 'Detection' and "Echocardiographic evaluation of the thoracic and proximal abdominal aorta".)

Vascular imaging — For those in whom vascular imaging was not completed, we obtain imaging (or completion imaging) to evaluate the aorta for potential embolic sources, from its origin to the femoral bifurcation, once it is safe to do so. (See "Thromboembolism from aortic plaque" and "Embolism from atherosclerotic plaque: Atheroembolism (cholesterol crystal embolism)" and "Clinical manifestations and diagnosis of thoracic aortic aneurysm", section on 'Imaging diagnosis'.)

Treatment

Operative treatment of suspected source — If valvular vegetations are diagnosed as the cause of the embolic event, valve replacement is strongly considered to prevent future embolic events, as well as to remove a potential source of infection. (See "Surgery for left-sided native valve infective endocarditis".)

Aneurysmal disease and large vessel atheroma/thrombus as etiologies of embolism can be treated with exclusion of the segment involved or open surgical bypass grafting. Open aortic aneurysm repair and aortobifemoral bypass have excellent durability. (See "Open surgical repair of abdominal aortic aneurysm".)

Open aortic thromboendarterectomy may be an option for patients with symptomatic mobile aortic thrombus, particularly for those located at or near the visceral segment of the abdominal aorta [50]. Although the optimal treatment strategy is not known for certain, intervention may offer better long-term outcomes. In one review comparing surgery with anticoagulation for mural thrombus in minimally atherosclerotic aortas, patients who had the thrombus removed had lower rates of persistent thrombus/recurrence (5.7 versus 26.4 percent) and lower rates of recurrent peripheral artery embolization (9.1 versus 25.7 percent compared with anticoagulation alone) [51]. (See "Thromboembolism from aortic plaque", section on 'Surgery'.)

For patients with popliteal aneurysm as the source of embolization, lower extremity bypass and exclusion of the aneurysm provide a durable revascularization. The patency rates for popliteal artery bypass are largely dependent on the quality of the available outflow [27,28]. (See "Surgical and endovascular repair of popliteal artery aneurysm", section on 'Surgical bypass'.)

Endovascular exclusion of suspected source — Techniques for endovascular treatment of aneurysmal and occlusive disease have been used for treating suspected sources of embolic disease to the lower extremities. Compared with open procedures, the general advantages include less pain, faster recovery time, and less perioperative morbidity and mortality. A combination of open and endovascular approaches can sometimes be used to treat multiple areas suspected to be sources of embolus [9].

Endovascular stent-grafts have been used to exclude thoracic or abdominal aortic and popliteal sources of lower extremity embolization. At all sites, adequate sealing above and below the affected area is necessary. When a stent-graft is used to cover an area that is suspected of having been an embolic source, it is important to avoid manipulations that may cause intraprocedural embolization. (See "Endovascular repair of the thoracic aorta" and "Endovascular repair of abdominal aortic aneurysm".)

To obtain vascular access during these procedures, open exposure of the femoral vessels has the advantage of being able to flush out debris that may have become dislodged during the conduct of the case prior to repairing the arteriotomy.

Surveillance imaging protocols following endovascular repair need to be followed as endoleaks or other late complications of endovascular intervention can occur.

Medical therapies

●Anticoagulation - We agree with multidisciplinary guidelines that recommend oral anticoagulation to prevent recurrent embolism after embolectomy [33]. Most patients will need to be anticoagulated for at least three months. For patients who do not have a surgically correctible cause of their embolic event, the benefits versus risk of anticoagulation need to be considered. Patients with ongoing atrial fibrillation and a prior embolic event are at a significantly increased risk of stroke or other embolic event and often warrant lifelong anticoagulation unless there is some other compelling factor. (See "Atrial fibrillation in adults: Use of oral anticoagulants".)

●Atherosclerosis risk reduction - Statins and antiplatelet agents such as aspirin appear to reduce the risk of atheroembolic events and are generally recommended for patients with coronary artery disease equivalents (ie, peripheral artery disease, aneurysmal disease). Regimens for developing plaque regression for reduced embolic events in the aorta are being investigated [52]. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk" and "Thromboembolism from aortic plaque", section on 'Treatment'.)

MORBIDITY AND MORTALITY — It is difficult to compare published results of the treatment of acute embolism resulting in ischemia because of different methods used to describe the severity of ischemia and differences in the duration of ischemia. However, it is clear that, in spite of optimal therapy, acute embolism is associated with high rates of morbidity and mortality [53,54]. Limb loss rates as high as 30 percent and hospital mortality as high as 20 percent have been quoted in surgical series [55-57]. A majority of amputations are above the knee.

Cardiopulmonary complications account for the majority of the deaths, underscoring the severity of the baseline medical condition of the typical patient. Approximately 15 to 20 percent of patients die within one year after presentation, usually from the medical illnesses that predisposed them to acute limb ischemia [58].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute extremity ischemia".)

SUMMARY AND RECOMMENDATIONS

●Clinical presentations – Clinical manifestations of acute embolism to the lower extremities can range from isolated digital ischemia to profound acute global limb ischemia. Some patients will experience a subclinical progressive loss of outflow vessels from recurrent embolism leading to a chronic peripheral artery disease-like picture. (See 'Clinical presentations' above.)

●Etiologies – A variety of etiologies (table 1) can potentially lead to embolization of the lower extremities, and understanding these should guide an efficient and thorough clinical evaluation, treatment, and source control. The history and physical examination may be sufficient to determine the most likely etiology and to initiate treatment. (See 'Etiology' above.)

●Vascular imaging – We suggest obtaining CT angiography because it provides valuable information about the location of the disease and level of baseline atherosclerotic plaque burden. Even in the setting of acute limb ischemia, CT angiography can usually be quickly accomplished while preparing the patient for intervention, but imaging can be deferred if it will delay treatment. (See 'Vascular imaging' above.)

●Initial management – For those who present with acute limb ischemia, anticoagulation typically with a heparin (bolus followed by infusion) and intravenous fluid therapy should be immediately initiated prior to making plans for intervention. These can be started while awaiting evaluation by a specialist trained to treat the embolic event. (See 'Initial management' above.)

●Approach to limb management – Options for managing lower extremity embolism include open embolectomy, thrombolysis, and transcatheter thrombectomy. Factors such as anatomy, degree of limb threat, runoff, suspected etiology, and patient factors will guide the choice of one over the other. (See 'Approach to limb management' above.)

•For patients without a femoral pulse who have a normal vascular exam on the contralateral side, open embolectomy is generally the best procedure, though exceptions may exist.

•For patients who have embolized or thrombosed their tibial runoff, transcatheter thrombectomy with or without thrombolytic therapy may improve outflow, leading to better options for subsequent open and/or endovascular revascularization.

•For patients whose history suggests that the embolic material is chronic thrombus (eg, mural thrombus from aneurysm, aortic thrombus) or nonthrombotic material (eg, tumor, embolized device fragments), open embolectomy or transcatheter embolectomy are better options compared with thrombolysis.

●Subsequent evaluation and treatment – Once the acute limb issues have been attended to, the subsequent diagnostic evaluation is focused on identifying the suspected embolic source, typically using echocardiography or additional vascular imaging. Once the source is known, additional intervention to remove or exclude the source from the circulation is generally preferred over anticoagulation alone. For patients with coronary heart disease equivalents, treatment with aspirin and statins should be a component of their medical therapy. (See 'Preventing future embolic events' above and 'Medical therapies' above.)