Embolism to the upper extremities

INTRODUCTION — Embolism to the upper extremities refers to the transit of material from a location outside the extremity into and lodging within one of the upper extremity arteries. The material may arise from any of a variety of sources and cause a spectrum of symptoms, ranging from no clinically appreciable downstream effects to acute and profound ischemia with the potential for amputation.

The clinical features, diagnosis, and management of embolism to the upper extremities is reviewed. Embolism affecting the lower extremity is reviewed separately. (See "Embolism to the lower extremities".)

UPPER EXTREMITY ARTERIAL ANATOMY — Perfusion to the upper extremity originates with the subclavian artery, branching off the innominate artery on the right and directly off the aortic arch on the left. Variations exist but occur infrequently (figure 1) [1].

Several branches arise from the proximal subclavian artery, including the vertebral artery, internal mammary artery, costocervical artery, and thyrocervical trunk. These branches supply the shoulder and ipsilateral chest wall (figure 2). As the subclavian artery passes over the first rib and behind the anterior scalene muscle, it becomes the axillary artery. The first part of the axillary artery, before it passes behind the pectoralis minor muscle, provides an inferiorly oriented superior thoracic artery. The second part of the axillary artery gives off the thoracoacromial artery and the lateral thoracic artery as it courses posterior to the pectoralis minor. The third part of the axillary artery, distal to the pectoralis minor muscle, provides three branches, including the subscapular artery and anterior and posterior circumflex humoral arteries.

Thereafter, the axillary artery transitions into the brachial artery, which first gives off the profunda brachii, superior and inferior ulnar collateral arteries, and finally divides into its terminal branches of the radial and ulnar arteries. Throughout the upper extremity, from subclavian to palmar arch, a collateral network provides redundancy of blood flow (figure 3A-C) [1-4].

Anatomic anomalies exist, including aberrations in the bony anatomy, which can affect the risk of embolization. As the subclavian artery arises from the thorax and enters the thoracic outlet, it crosses over the first rib. In less than 1 percent of the population, a cervical rib is present (figure 4 and image 1), originating from the seventh cervical vertebrae. When present, it is sometimes long enough to fuse to the first rib [5]. These occasional bony anomalies are associated with arterial thoracic outlet syndrome and have bearing on the risk of embolization. In the presence of these anatomic aberrations, the rich collateral circulation to the upper extremity can mitigate the ischemic consequences of embolic phenomenon.

ETIOLOGIES — Emboli to the upper extremities originate from a variety of sources (table 1), usually with an acute clinical presentation [6-8]. Among those with acute limb ischemia (ALI), involvement of the upper extremity comprises less than 25 percent [6,9,10]. Of these patients, over half are due to embolism. Relative to the incidence of embolic phenomena to the lower extremities, there is a paucity of data regarding etiologic incidence for embolism to the upper extremity.

Cardiac sources — Cardiac sources of all types comprise the majority of inciting causes and warrant prime consideration when evaluating sources of emboli [11,12]. Upper extremity emboli can arise from thrombus due to stasis or from anatomic aberrations.

Atrial fibrillation — Among patients who present with upper extremity ALI with an embolic etiology, approximately 60 percent will have atrial fibrillation [11,13]. In the presence of a fibrillating heart, the ejection fraction diminishes, providing an opportunity for thrombus to form and subsequently travel distally. The risk of systemic embolization is lower among patients with paroxysmal atrial fibrillation compared with patients with a sustained arrhythmia [13]. Among those with atrial fibrillation as the source for embolism, females tend to be at greatest risk of needing intervention for embolic sequelae, even after adjustment for age and associated comorbidities [13]. (See "Mechanisms of thrombogenesis in atrial fibrillation".)

Postmyocardial infarction thrombus — The development of diastolic dysfunction and left ventricular aneurysms after an acute myocardial infarction (MI) creates circumstances whereby left ventricular thrombus can form, which can then embolize distally [14]. Left ventricular aneurysms are more common among patients who experience anterior ST-segment elevation MIs, thus making this a target for surveillance. (See "Left ventricular thrombus after acute myocardial infarction".)

Patent foramen ovale — The occurrence of a patent foramen ovale (PFO) has also been implicated in association with systemic arterial embolization [15,16]. The foramen ovale is a necessary pathway formed in utero between the right and left atria that allows oxygenated blood from the placenta to reach the fetal arterial circulation. Its presence becomes pathologic when it persists beyond birth and causes complications, since it acts as a conduit for material from the venous circulation to cross into the systemic arterial circulation (ie, paradoxical embolism). In the general population, the incidence of PFO is approximately 0.2 percent, with only a small minority ever experiencing thromboembolic complications as a result [17].

Atrial myxoma — Embolic material from cardiac myxoma, which is an uncommon primary cardiac malignancy, occurs when tumor cell fragments break away from the intracardiac mass and travel through the systemic arterial circulation. Although rare, myxomas more commonly arise in the left heart than in the right, ensuring a direct path beyond the aortic valve to various systemic vascular beds [18,19]. (See "Cardiac tumors", section on 'Myxomas'.)

Proximal arterial sources

Atheromatous debris — Atheromatous debris that collects on any arterial wall proximal to the upper extremity can be a source of upper extremity thromboembolism. Atheromatous material in the ascending aorta, aortic arch vessels (ie, brachiocephalic [innominate], left/right subclavian arteries) are high-risk locations for upper extremity embolism that also have a risk for stroke when embolism occurs [20,21]. (See "Embolism from atherosclerotic plaque: Atheroembolism (cholesterol crystal embolism)" and "Thromboembolism from aortic plaque".)

In addition, aneurysm of an upper extremity artery can form thrombus due to turbulent flow dynamics. Thrombus in an aneurysm proximal to the upper extremity may harbor embolic potential. While spontaneous upper extremity peripheral aneurysms account for less than 1 percent of all peripheral arterial aneurysms, innominate and subclavian aneurysms tend to occur with slightly greater frequency [22]. (See "Overview of aneurysmal disease of the aortic arch branches or upper extremity arteries in adults".)

Iatrogenic causes — Among non-native arterial sources, surgically placed conduits proximal to or within the upper extremities can bear thrombus that can dislodge into the circulation of the upper extremities. Clot and atherosclerotic debris in the proximal anastomosis of an axillary-to-femoral bypass, in carotid-to-subclavian bypass, or within a thrombosed arteriovenous (AV) fistula or AV graft can contain embolic material for distal embolization (image 2) [23]. If these surgically created conduits thrombose, they are generally left in situ, rarely causing embolization distally, but if embolism does occur, they may require ligation or explantation.

Arterial thoracic outlet syndrome — In the presence of a congenital or acquired bony abnormality of the thoracic outlet, in particular a cervical rib or clavicular fracture, anatomic aberrations of the subclavian artery can form. Consequences of arterial thoracic outlet syndrome (TOS) can include subclavian artery dilation and aneurysm, stenosis, and ulceration of the subclavian artery, all of which have the potential for thromboembolic complications to the upper extremities. Less frequently, retrograde thromboembolism can occur via the vertebral artery, leading to posterior stroke [24,25]. (See "Overview of thoracic outlet syndromes", section on 'Arterial TOS'.)

Another entity known as vascular quadrilateral space syndrome is associated with upper extremity embolism. This syndrome has been observed in individuals who regularly perform repeated overhead motions, as with some patients who develop TOS. In contrast to arterial TOS, repetitive vascular trauma associated with quadrilateral space syndrome leads to aneurysmal degeneration or dissection of the circumflex humeral branch of the axillary artery, creating potential for distal embolization [26].

Less common etiologies

Traumatic injury — Upper extremity trauma can manifest with various vascular sequelae, including aneurysmal degeneration of an injured segment of artery [27]. Over time, as arterial aneurysms of the proximal upper extremity expand, they can rupture or develop mural thrombus, which can be a source of thromboembolism with potential for upper extremity ischemia [28]. In addition, while traumatic pseudoaneurysm, dissection, occlusion, or arteriovenous fistula of the subclavian, axillary, or brachial arteries may not always have immediate consequences for limb perfusion, they can manifest with complications including upper extremity ischemia in a delayed setting [29].

Hypercoagulable states — Several hypercoagulable conditions exist that create an environment conducive to clot production. In one review, the development of floating thrombus in the proximal upper extremity arteries was greatest among those with hypercoagulable states, malignancy, chronic tobacco abuse, trauma, and vasculitis [20].

While heritable and acquired thrombophilias (table 2) are predominantly associated with venous thromboembolism, some have been implicated in the pathogenesis of arterial ischemia.

●Among heritable conditions, factor V Leiden, prothrombin G20210 mutation, and deficiencies of protein C and protein S have been associated with an increased risk of ischemia in arterial beds [30,31].

●Acquired thrombophilias that should be considered after an ischemic event, particularly in young patients without overt risk factors, include antiphospholipid syndrome, heparin-induced thrombocytopenia, myeloproliferative neoplasms, and paroxysmal nocturnal hemoglobinuria [32].

●With regard to myeloproliferative neoplasms, both the neoplastic state as well as some of the pharmacologic agents used to treat them can increase the risk of arterial ischemic complications [33,34].

In addition, while arterial complications have been less frequently observed compared with venous complications in patients with coronavirus disease 2019 (COVID-19), activation of the coagulation cascade is common among both [35]. A proinflammatory state causes a cytokine storm and activation of the endothelial cells with resultant endothelial dysfunction, setting up a condition conducive to thrombus generation and downstream embolization [36]. The hypercoagulability can impact multiple extremities, causing simultaneous ischemia in multiple limbs [37]. (See "COVID-19: Acute limb ischemia".)

CLINICAL EVALUATION — The patient with suspected embolism to the upper extremity typically presents with a history of sudden onset of symptoms [38]. It is uncommon for patients to have an indolent presentation for upper extremity ischemia, since atherosclerotic disease affects the upper extremity at a much lower rate compared with the lower extremity [7,39]. Nevertheless, the provider should still ascertain the baseline neurovascular status of the affected extremity.

In the setting of acute limb ischemia, the clinical evaluation should proceed in an expeditious manner, as the likelihood of recovery largely depends on prompt and complete upper extremity revascularization [38]. Even among those with a history of a more indolent onset of symptoms, prompt evaluation and treatment aims to preserve perfusion to mitigate the risk of future critical ischemia [4].

History — History-taking should be thorough, albeit efficient, looking also into possible risk factors for thromboembolism. (See 'Etiologies' above.)

Classic findings on patient history that arouse suspicion of upper extremity arterial embolism include complaints of a sudden onset of upper extremity pain, numbness, loss of color (ie, pallor), coolness to the affected extremity, and possibly reduced motor function or paralysis [11,38]. The patient is often able to clearly communicate the precise time of the onset of symptoms [4]. (See "Overview of upper extremity ischemia", section on 'Acute ischemia'.)

Given the frequency with which a cardiac etiology is implicated as the source of embolism, any history of cardiac arrhythmia, coronary artery disease, myocardial infarction, or valvular pathology should be noted [11,12]. In the case of a patient on anticoagulation, such as those prescribed it for a cardiac indication, an assessment of medication compliance should be sought. Subtherapeutic international normalized ratios (INRs) with nonvalvular atrial fibrillation are associated with an increased risk of systemic embolization [9,16].

In addition to cardiac etiologies, patients should be questioned about any history of proximal aortic or great vessel disease or prior endovascular or surgical intervention. Specific information about known aortic aneurysmal disease or aortic dissections should be elicited, as well as any history of surgical intervention. Known personal or family history of hypercoagulable disorders or risk factors for hypercoagulability, such as smoking status or presence of malignancy, should also be determined.

Physical examination — A complete examination of the patient, with a focus on the cardiovascular system, should be performed. The symptomatic extremity may demonstrate a cool, pale arm. Distal arterial Doppler signals will typically be absent in the acutely ischemic arm, with preservation of the venous Doppler signals until the ischemic state has progressed to the point of irreversibility. A sensorimotor exam facilitates classification of acute ischemia (table 3).

Sensory deficits, or an absence thereof, suggest the initial stages of ischemia, whereas manifestation of motor deficits represents an immediately threatened arm in need of emergency revascularization [40]. Additional physical findings, which may be of greatest diagnostic benefit in the setting of more distally lodged emboli, can include poor capillary refill at the fingertips, lack of Doppler signals in the hand, and a digit brachial index less than 0.7. (See "Noninvasive diagnosis of upper and lower extremity arterial disease", section on 'Wrist-brachial index' and "Noninvasive diagnosis of upper and lower extremity arterial disease", section on 'Digit waveforms'.)

Throughout the examination of the affected extremity, comparison to the unaffected extremity may provide a means of comparison to the patient's approximate baseline neurovascular status.

Laboratory studies — Laboratory studies are not specific for the diagnosis of arterial embolism. Certain studies can be followed to trend the systemic effects of progressive ischemia.

Depending on the duration of symptoms, the patient may have leukocytosis, increased lactic acid level, and elevated inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein. D-dimer has good negative predictive value in the setting of arterial ischemia but is of unclear significance when found to be elevated [41]. None of these laboratory values are specific to arterial ischemia but provide corroboratory evidence to suggest a proinflammatory state [42].

Because the patient must be initiated on therapeutic anticoagulation, baseline coagulation studies should be obtained. In addition to prothrombin time, activated partial thromboplastin time, and INR, a fibrinogen level will be necessary if thrombolytic therapy will be used.

In patients who report compliance with a factor Xa inhibitor, thromboelastogram or rotational thromboelastometry can be of use to determine the risk of potential bleeding [43,44].

In addition, because therapeutic endeavors may require angiography with the administration of iodinated contrast, a basic metabolic profile including serum creatinine and blood urea nitrogen will provide an assessment of current renal function.

Lastly, a blood type and screen are imperative prior to any operative intervention.

Vascular imaging — The decision to pursue vascular imaging is based upon the level of suspicion regarding the diagnosis of arterial embolism and the need for information to guide preprocedure planning. Multiple imaging modalities exist, each with individual merits and drawbacks. Computed tomographic (CT) angiography is typically the preferred means of initial imaging (image 2), as it provides information about the entire arterial tree over the extent of the diagnostic images and will also detail the surrounding structures with good resolution in cases in which a broad differential diagnosis exists.

CT angiography can be completed quickly, which is a significant benefit in patients with acute limb ischemia. Although the upper extremity arterial circulation can generally be seen with the CT angiography, its sensitivity for the distal arterial branches may be diminished. This is of particular concern when the transit of contrast is impeded by the presence of embolus or chronic atherosclerotic plaque. Notwithstanding the need for a large contrast bolus with its potential nephrotoxic effects, CT angiography can provide a detailed roadmap for surgical planning, localizing the sites of embolic fragments, presence of coexisting atherosclerotic disease, targets for possible bypass, and any coexisting pathology that may have been the source of emboli [45].

Duplex ultrasound has been used in the context of suspected arterial thromboembolism to image the arterial segments of greatest concern, most often when the risk of large-dose contrast administration is prohibitive. While duplex ultrasound negates the need for contrast, it may not be as readily available as CT angiography, requires a longer time to obtain images of adequate quality, and is largely operator dependent. Ultrasonography has the benefit of demonstrating dynamic flow characteristics and can provide a better sense of the distal arterial circulation, even in the presence of proximal embolic or atherosclerotic disease [12].

Magnetic resonance (MR) angiography is generally not the optimal study in suspected arterial embolism to the upper extremity and is not typically selected as the initial imaging modality. In the setting of acute limb ischemia, MR angiography may require a prohibitively long time to complete. While it negates the need for iodinated contrast as used for CT angiography, the administration of gadolinium as a contrast agent has the associated risk of nephrogenic systemic fibrosis in patients with renal disease [46]. Moreover, the spatial resolution and ability to discern detail in areas of arterial disease are limited.

Although not typically used as the first means of imaging, digital subtraction angiography is frequently used for intraoperative imaging when angiography is needed to guide therapeutic maneuvers. Contrast administration is necessary but can be given in small volumes while focusing on localized arterial segments, providing a focal assessment of flow dynamics and the pattern of disease from various angles.

INITIAL MANAGEMENT — The approach to management is first and foremost guided by the acuity of presentation and patient symptoms [40]. The pace at which therapy must progress depends on the patient's neuromuscular exam. A patient with absent distal Doppler signals and ipsilateral sensorimotor deficits must be revascularized with greater expediency compared with a patient with preserved distal arterial Doppler signals and no sensorimotor deficits.

Anticoagulation — As soon as acute arterial embolism to the upper extremity is suspected, systemic anticoagulation should be initiated. Anticoagulation minimizes propagation of ongoing thrombosis. Because of its short half-life and readily available means of monitoring at point of care, unfractionated heparin is usually chosen for initial anticoagulation, an alternative agent for those with contraindications. It is administered first as an intravenous bolus (80 units/kg), followed immediately by continuous infusion (18 units/kg/hr). The partial thromboplastin time is monitored perioperatively, and during interventions, the activated clotting time is monitored to ensure full anticoagulation.

A history of chronic anticoagulation, particularly when an elevated coagulation profile is noted preoperatively, may prompt consideration for reversal of the long-acting anticoagulants concomitant with initiation of short-acting unfractionated heparin. Regardless of reported compliance with chronic anticoagulation, or the lack thereof, an accurate assessment of present anticoagulation via a preoperative coagulation profile is useful [44]. Knowledge of the baseline level of anticoagulation may suggest why the patient had a thromboembolic event. Additionally, transitioning from a long-acting agent to a short-acting one improves the ability to control surgical bleeding in the operating room [43]. At times, use of fresh frozen plasma, prothrombin complex concentrate, idarucizumab, or andexanet alfa may be necessary to preoperatively ensure surgical hemostasis.

APPROACH TO LIMB MANAGEMENT — Management of arterial embolism to the upper extremity largely depends on etiology, location of thromboembolic debris, previous interventions and scars, and availability of endovascular resources. Factors specific to the upper extremity include its proximity to the aortic arch and great vessels, the presence of collateral pathways within the arm, and the potential for significant debilitation that can result if revascularization is unsuccessful.

Revascularization — For patients with a marginally or immediately threatened upper extremity (table 3), revascularization should be promptly pursued. There are very few contraindications to operative intervention (ie, too physiologically or hemodynamically unstable), and delayed revascularization can result in severe functional impairments.

Revascularization should also be considered in the presence of a clinically viable extremity (table 3)[4]. Although the upper extremity has a rich collateral network that can compensate for an acutely occluded vessel, prolonged perfusion impairments can eventually lead to the onset of functional impairments and ischemic contracture. Moreover, compensatory increases in flow through one collateral pathway can accelerate atherosclerosis in that artery, increasing the pace at which chronic vascular insufficiency develops.

Open versus endovascular — Open thromboembolectomy is the most commonly used method of revascularization for patients with acute upper extremity ischemia, particularly in institutions with limited endovascular resources. Open thromboembolectomy is preferentially performed for several reasons:

●The majority of emboli lodge in the distal brachial artery (image 3), which can generally be exposed quickly given relatively limited amount of overlying soft tissue [7,10].

●Brachial embolectomy can often be performed using local anesthesia.

●Even at more proximal or distal upper extremity arterial sites, surgical exposure of the upper extremity arteries is generally straightforward [7,10].

●Wound complications are uncommon in the upper extremity because incisions are outside of skin folds in non-hair-bearing areas that can be easily monitored during hospitalization and by the patient after discharge.

However, open surgical exposure is not without morbidity, including pain, the risk of damage to surrounding neurovascular structures, and the risk of subsequent thrombosis due to manipulation during the procedure despite best efforts to maintain patency.

Endovascular techniques are being used with increasing frequency. However, the delayed clearance of thrombotic material such as during catheter-directed thrombolysis can be prohibitive in acutely ill patients, particularly in those with multiple comorbidities, and in those with an immediately threatened upper extremity. The majority of endovascular interventions are performed using percutaneous access, commonly achieved at the femoral vessels in the groin. Options for percutaneous access are limited if vascular patency is poor or atherosclerotic disease burden is extensive throughout the femoral, iliac, aortic, and subclavian vessels. Endovascular procedures can be easily performed under local anesthesia, which is an advantage particularly in a patient with significant physiologic derangements. Risks associated with endovascular intervention include vessel injury such as dissection and perforation, potential nephrotoxicity related to contrast administration.

Often, open surgical and endovascular approaches (ie, hybrid procedure) can be used in the same operative setting, providing complementary information and therapeutic maneuvers. Still, the surgeon needs to weigh the risks and benefits of each approach prior to committing a patient to one therapeutic modality or another.

Reperfusion and potential need for fasciotomy — After revascularization, reperfusion of the upper extremity may result in significant swelling. This is of particular concern when the limb has remained ischemic for a prolonged time [38]. Upon revascularization, various inflammatory processes ensue. These include activation of immune-mediated cells, release of oxygen-free radicals, and overwhelming of innate mechanisms that control antioxidants, metabolize carbon dioxide, and limit endothelial damage.

Compartment syndrome will ultimately develop if these inflammatory processes continue, causing swelling of the surrounding tissues within their fascial compartments. If unabated, the swelling can cause muscular compromise, cessation of venous outflow, and ultimately cessation of arterial inflow. (See "Acute compartment syndrome of the extremities".)

Therefore, with ischemia of prolonged duration, compartment release after revascularization by means of prophylactic fasciotomies should be strongly considered. (See "Upper extremity fasciotomy techniques", section on 'Impending'.)

In the upper extremity, if fasciotomies are not performed in the index setting, the volar, dorsal, and hand compartments should be monitored closely for compartment syndrome and the need for fasciotomy.

Nonviable extremity — When clinical evaluation has deemed the upper extremity to be irreversibly ischemic, attempts at revascularization have the potential to cause severe metabolic disturbances with associated cardiovascular and hemodynamic consequences. Exam findings concerning for irreversibility of ischemia include a mottled arm without pulses or sensation and muscle rigor (table 3). Expeditiously performing an amputation in this setting may be the safest option. This occurrence is quite rare but should be recognized prior to attempts at revascularization, as the benefit of revascularization might be far outweighed by the hemodynamic consequences. (See "Upper extremity amputation".)

TECHNIQUES — Surgical embolectomy, thrombolysis, and transcatheter embolectomy are tools that are used with varying frequency to clear embolic debris from the upper extremity. Open embolectomy is the most common means of restoring perfusion to the upper extremity but is frequently combined with endovascular techniques in a hybrid approach to provide best outcomes.

Open thromboembolectomy — Open thromboembolectomy has historically been the standard approach to upper extremity revascularization for acute limb ischemia of embolic origin. Even with progressive advancements in endovascular tools and techniques, open thromboembolectomy represents the most straightforward and immediate means of restoring perfusion in most such patients.

Distal brachial embolectomy — When embolic debris has lodged in the upper extremity arteries distal to the axillary artery, the most advantageous site of exposure for access in anticipation of a mechanical thromboembolectomy is at the brachial bifurcation. At this site, the surgeon can easily direct a Fogarty balloon catheter into the brachial artery and its branches. The placement of a three-centimeter transverse skin incision overlying the brachial bifurcation can be facilitated by identification of bony landmarks in close proximity to the bifurcation on preoperative cross-sectional imaging or by performing a duplex ultrasound of the extremity while the patient is on the operating room table. Use of imaging to assist with placement of the initial incision is helpful, as deviations from normal brachial artery bifurcation patterns occur in approximately 30 percent [47]. Thereafter, dissection is carried out onto the neurovascular structures, opening the brachial sheath. The brachial, radial, and ulnar arteries are isolated and controlled.

If not previously given, a bolus of heparin should be administered to a goal activated clotting time greater than 250 (may vary depending on institutional calibration).

Creation of a transverse arteriotomy in the anterior brachial artery allows for primary closure after completion of the embolectomy. However, in the presence of significant disease in the brachial artery, a longitudinal incision can be made with later closure using patch angioplasty to reduce the risk of flow-limiting stenosis. Passage of a #3 Fogarty balloon catheter up the brachial artery and a #2 Fogarty catheter down each forearm branch vessel will allow extraction of embolic material. Caution is advised because the balloon catheter can cause intimal trauma and dissection when pushed or pulled against resistance. It is important not to overinflate the balloon. Therefore, any resistance must be appreciated and responded to as the catheter passes intraluminally. At least two passages of the catheter should be performed with no intraluminal thromboembolic debris extracted and adequate backbleeding from the vessel obtained in order to have confidence in the success of treatment. Once balloon catheters are passed in each direction with return of brisk backbleeding, the arteriotomy is closed, and the distal pulses are reevaluated. If adequate backbleeding is not appreciated, a thrombolytic agent (eg, tissue plasminogen activator, streptokinase) can be used to directly clear any residual thrombus [48]. Completion digital subtraction angiography confirms clearance of the embolic burden after embolectomy and arteriotomy closure (image 4) or can assist with identifying the reason for an unsatisfactory embolectomy. Angiographic findings of vasospasm can be treated with intra-arterial injection of nitroglycerin or papaverine.

Areas of chronic disease may necessitate balloon angioplasty, stenting, or open intervention. If flow terminates prematurely and cannot be otherwise restored to the end arteries, radial or ulnar cutdown may be necessary to remove resistant thrombus. Alternatively, a bypass with or without patch angioplasty may become necessary to adequately revascularize the extremity. Such situations are uncommon given the relative rarity of atherosclerotic peripheral artery disease affecting the upper extremity.

Other sites — Embolic debris lodged at sites proximal or distal to the brachial artery can still be accessed and extracted through an arteriotomy adjacent the brachial bifurcation using appropriate length and caliber Fogarty embolectomy catheters. However, when complete clearance of debris is unable to be performed through this site, alternative or additional incisions can be made overlying the area of concern.

Furthermore, if an obvious source of embolic material is identified pre- or intraoperatively (eg, thrombus from occluded bypass graft), therapeutic maneuvers such as surgical ligation or removal of a thrombosed bypass graft should be anticipated to minimize the risk of further embolization from this site. The etiology of embolism is not frequently identified in the preoperative setting, and any surgically treatable etiology is often treated in a staged fashion.

Catheter-directed thrombolysis — Catheter-directed thrombolysis has not been used as often as open embolectomy for revascularization of the upper extremity, although it represents an acceptable alternative for patients with very early stages of ischemia (table 3) [11,12]. The thrombolytic agent must infuse through the intraluminal catheter for 24 to 48 hours to have the greatest effect in clot clearance, which is much longer compared with open brachial thromboembolectomy. Thus, this is appropriate only for patients with a viable or marginally threatened extremity. Techniques for thrombolysis are reviewed separately. (See "Intra-arterial thrombolytic therapy for the management of acute limb ischemia".)

Depending on the embolic source, placement of a sheath and thrombolysis catheter in the thoracic aorta may contribute more risk than benefit. Wire manipulation in the presence of an aortic atheroma may cause further embolism. In addition, retraction of the lysis catheter and sheath from its original position embedded in the thromboembolic site in the upper extremity poses the risk of intracranial bleeding from flow of the thrombolytic agent into the intracranial circulation. Nevertheless, catheter-directed thrombolysis remains an alternative for patients whose exam does not demonstrate an immediately threatened limb and whose arterial circulation proximal to the extremity has a very limited amount of atherosclerotic disease.

Transcatheter embolectomy — Transcatheter embolectomy does not require pharmacologic thrombolytic agents or a prolonged duration of intraluminal device positioning. This reduces some of the risks inherent to pharmacologic thrombolysis while avoiding the potential morbidity of open surgery. This approach is used with increasing frequency and can be easily combined with other endovascular tools to provide clearance of embolic debris and correction of underlying disease to revascularize the upper extremity.

Transcatheter embolectomy still requires passage of an intraluminal device in or adjacent the aortic arch, with its implicit risk of further embolization in the presence of aortic atheroma (cerebral, extremity). Vascular access is obtained percutaneously using ultrasound guidance, typically at the common femoral artery, and a wire and aspiration device are passed to the affected upper extremity. A suction effect is created just proximal to the site of embolic obstruction.

PREVENTION OF FUTURE EMBOLIC EVENTS — The completion of a thorough investigation of all possible embolic sources should be performed after the upper extremity has been reperfused, if not completed before or during revascularization. While usually initiated prior to surgical intervention, ensuring a comprehensive assessment of the various possible sources will direct subsequent treatment to correct the etiologic source and minimize the risk for future embolic events.

●Echocardiography – Because of the frequency with which embolic material originates in the heart, an echocardiogram is a critical component of every embolic work-up. Thrombus, masses, and valvular abnormalities, including vegetations, can be seen. Echocardiography can be performed concomitantly with the index operation using transesophageal echocardiography, depending on local resources and expertise. (See "Echocardiography in detection of cardiac and aortic sources of systemic embolism".)

A decision regarding medical treatment (eg, chronic anticoagulation) or intervention for identified cardiac pathologies can be made while the patient is recovering from the revascularization procedure, taking into account the extent of any future intervention, patient comorbidities, and anticipated tolerance for a cardiac procedure.

●CT angiography – Proximal arterial sources should be identified with a CT angiogram, if not already performed as a part of the initial work-up. Identification of an embolic source in the ascending aorta or aortic arch may warrant either open surgery, endovascular stent grafting, or nonoperative management with antithrombotic therapy alone. Endovascular stent-grafting of the ascending aorta (including aortic arch segment) is limited to select centers. (See "Endovascular repair of the thoracic aorta".)

Suspicion of vascular quadrilateral space syndrome should also prompt CT angiography, if not already performed, to identify any aneurysm involving the circumflex humeral branch of the axillary artery. This would ultimately require ligation or embolization of the branch.

●Chest radiography – Obtaining a chest radiograph can sometimes identify a bony abnormality of the thoracic outlet, as seen in patients with thoracic outlet syndrome, and would prompt a search for adjacent anatomic abnormalities.

Diagnosis of arterial thoracic outlet syndrome warrants additional thoracic outlet decompression and aneurysm repair [24,25]. Compressive syndromes (including quadrilateral space syndrome) are typically managed in a staged fashion following the index revascularization procedure [24,26].

●Hypercoagulable evaluation – Laboratory evaluation looking for hematologic abnormalities causing hypercoagulability should be simultaneously undertaken, particularly if no underlying anatomic lesion is uncovered by imaging [49]. Comprehensive laboratory work-up should include lupus anticoagulant, anticardiolipin antibodies, homocysteine, prothrombin G20210A, factor V Leiden, protein C and S levels, and antithrombin level. Although the prevalence of venous thromboembolism is much greater with these thrombophilias, a hypercoagulable state should be suspected in the young patient without other risk factors for acute arterial embolic ischemia [31]. Given the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the midst of a global pandemic, real-time reverse transcription polymerase chain reaction assay should also be undertaken to assess for COVID-19 positivity [50]. If arterial thromboembolism occurred during or shortly after exposure to heparin with a simultaneous 50 percent decrease in platelet count, heparin-induced thrombocytopenia should be considered with corresponding laboratory evaluation performed. When a heritable hypercoagulable disorder is identified, the patient may require lifelong anticoagulation unless a contraindication is identified or arises.

MORBIDITY AND MORTALITY — Mortality following upper extremity arterial thromboembolism varies widely given the array of clinical presentations and treatments. In one study among patients who underwent surgical embolectomy under local anesthesia, perioperative (30-day) mortality was 9 percent, and during follow-up, 63 more patients died, culminating in a greater than 50 percent long-term mortality [48]. Seven patients required reintervention, and two ultimately required amputation. This high mortality rate in this study and others is generally reflective of the burden of baseline comorbidities and risk factors provoking thrombosis and embolization to the upper extremity [9,48].

The acutely ischemic arm has a significant compensatory mechanism via its collateral arterial networks; still, historical practice suggests that evaluation and initiation of treatment should be performed within six hours of symptom onset for the best outcomes. Among patients who survive, neuromuscular function of the upper extremity may be chronically impaired. Upper extremity exertional fatigue and ischemic contractures can develop. In a small minority, digital amputation may be necessary after revascularization of the extremity. (See "Surgical reconstruction of the upper extremity" and "Upper extremity amputation".)

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

●Arterial thromboembolism – Arterial embolism to the upper extremity most frequently presents acutely and accounts for approximately 25 percent of all acute limb ischemia events. Typical clinical manifestations include a sudden onset of pain, coolness to the extremity, pallor, loss of pulses, paresthesias, and paralysis, if allowed to progress. (See 'Introduction' above and 'Clinical evaluation' above.)

●Etiologies – Cardiac etiologies account for the majority of emboli traveling to the upper extremity. Other proximal arterial sources, iatrogenic etiologies, and hypercoagulability may predispose to embolism in the absence of a cardiac source. Infection with SARS-CoV-2 has arisen as a potential provoking cause of arterial thromboembolism. (See 'Etiologies' above.)

●Clinical evaluation and vascular imaging – The clinical evaluation should proceed in an expeditious manner. CT angiography is the preferred initial imaging modality for identification and localization of embolic debris, sources of embolism, presence of chronic arterial disease, and optimal sites of access and planning for intervention. (See 'Vascular imaging' above.)

●Anticoagulation – Initial management of upper extremity embolism begins with therapeutic anticoagulation to prevent the propagation of thrombus while preoperative planning is being undertaken. (See 'Anticoagulation' above.)

●Upper extremity revascularization – For upper extremity embolism, we suggest open thromboembolectomy, rather than percutaneous methods for revascularization (Grade 2C). Open thromboembolectomy can be quickly performed typically using an incision overlying the brachial artery bifurcation. Passage of embolectomy catheters proximal and distal effectively removes thrombus and debris. Catheter-directed thrombolysis and transcatheter embolectomy are alternative methods that require additional time that can be prohibitive for patients with a threatened upper extremity (table 3). (See 'Distal brachial embolectomy' above.)

●Fasciotomy – Prophylactic fasciotomies may be indicated to prevent the development of compartment syndrome depending on the duration of ischemia and progress of symptoms prior to revascularization. (See 'Reperfusion and potential need for fasciotomy' above.)

●Preventing future embolic events – After upper extremity revascularization, identification of the origin of embolic debris with further imaging and laboratory evaluation should be completed with subsequent staged intervention, when indicated, to mitigate the risk of future embolic events. (See 'Prevention of future embolic events' above.)