Overview of upper extremity ischemia

INTRODUCTION — The clinical presentation of upper extremity ischemia is varied and depends upon the level of the underlying disease, which can be classified as large vessel disease (acute or chronic arterial occlusive disease proximal to the wrist) versus small vessel disease (chronic arterial occlusive disease distal to the wrist). The large number of disease entities affecting the small vessels of the upper extremity (eg, arteritis, vasospasm) makes the clinical evaluation of upper extremity ischemia somewhat more complex compared with ischemia affecting the lower extremity.

As with the lower extremity, upper extremity ischemia can be due to a sudden (ie, acute) or gradual (ie, chronic) loss of blood flow. Acute ischemia is defined as having an onset of symptoms of less than two weeks. Acute upper extremity ischemia is typically due to thromboembolic complications from an underlying disease. Chronic upper extremity ischemia is related to progressive arterial narrowing. Acute thrombosis of an already narrowed segment can also occur (ie, acute-on-chronic ischemia).

Amputation related to ischemia is far less common in the upper compared with lower extremity. In 2005, among the 1.6 million persons living with a "loss of a limb," an estimated 573,000 had an upper extremity amputation [1]. Only 8 percent were categorized as a major amputation. Trauma accounted for the majority of major upper extremity amputations, while vascular diseases accounted for only 12 percent. Upper extremity ischemia in the pediatric population is even rarer and is often associated with upper extremity injury [2].

The clinical features, diagnosis, classification, and approach to treatment of acute upper extremity ischemia are reviewed. Acute lower extremity ischemia is reviewed separately. (See "Clinical features and diagnosis of acute lower extremity ischemia".)

UPPER EXTREMITY ANATOMY — The subclavian arteries provide blood flow to the upper extremities. On the left, the subclavian artery originates directly from the aortic arch distal to the left common carotid artery. On the right, blood flows first through the innominate (brachiocephalic) artery, which divides into the right common carotid artery and right subclavian artery (figure 1). The anatomy of the aortic arch can vary (figure 2) and may include an anomalous origin of the subclavian arteries. (See "Vascular rings and slings" and "Approach to the evaluation of dysphagia in adults", section on 'Cardiovascular abnormalities'.)

The subclavian artery passes over the first rib posterior to the anterior scalene muscle (figure 3) and becomes the axillary artery at the lateral margin of the first rib. The first part of the axillary artery is close to the chest wall and medial to the pectoralis minor muscle. The second part of the axillary artery is located deep to the pectoralis minor, and the third portion is lateral to the pectoralis minor. The axillary artery becomes the brachial artery (figure 4) at the lower margin of the teres major muscle. The brachial artery passes between the biceps and triceps muscles, accompanied by the ulnar and median nerves adjacent to the humerus, and supplies the soft tissues of the arm (figure 5). In the antecubital fossa, the brachial artery divides (figure 6) into the radial, interosseus, and ulnar arteries to supply the soft tissues of the forearm (figure 7). Distally at the wrist, the ulnar artery and radial artery supply the hand (figure 8).

The upper extremity veins are divided into the superficial and deep systems. The deep veins of the upper extremity include the paired ulnar, radial, and interosseous veins in the forearm; paired brachial veins of the upper arm leading to the axillary vein. The axillary vein becomes the subclavian vein at the lower border of the teres major muscle (figure 9). The main superficial veins of the upper extremity include the cephalic, basilic, median antebrachial, median antecubital, and accessory cephalic veins (figure 10). These superficial upper extremity veins serve as the mainstay for arteriovenous access creation in the dialysis-dependent patient.

The bones of the upper extremity include the humerus, radius, ulna, wrist bones, and phalanges. The musculature (figure 7) is contained within defined anterior and posterior compartments (figure 11 and figure 12 and figure 13 and figure 14).

The brachial plexus is formed by the ventral rami of the lower cervical and upper thoracic nerve roots (figure 15A-B). It supplies cutaneous (figure 16) and muscular innervation to the upper extremity (figure 5). The cords of the brachial plexus contribute to each of the five major nerves of the upper extremity (axillary, musculocutaneous (figure 17), radial (figure 18), median (figure 19), and ulnar (figure 20)). The axillary nerve is purely sensory.

Collateral circulation — The collateral circulation around the shoulder is usually sufficient to compensate for a focal area of chronic stenosis in the subclavian artery. When the proximal subclavian artery is occluded, blood flow is maintained to the arm via connections between the vertebral arteries (figure 21), superior and inferior thyroid arteries; intercostals, superior epigastric, and internal thoracic arteries; profunda cervicis and descending branch of the occipital artery; scapular branches of the thyrocervical trunk and the branches of the axillary artery; and the thoracic branches of the axillary artery with the aortic intercostals (figure 22) [3].

Similarly, the collateral circulation around the elbow compensates for reduced flow in the brachial artery with lesions that occur at the level of the elbow. The collateral circulation around the elbow includes contributions from the radial recurrent arteries medially, the anterior and posterior ulnar recurrent arteries and the inferior and superior ulnar collateral arteries medially, and the deep brachial and dorsal interosseous arteries (figure 23). 

The dual blood supply (radial, ulnar arteries) protects the hand somewhat (figure 24 and figure 8) [4]. The hand collateral flow has large variations (figure 25); however, a complete deep palmar arch is common (in up to 90 percent) [4].

INCIDENCE AND ETIOLOGIES — The upper extremity accounted for an average of 17 percent (range 7 to 32 percent) of cases of acute limb ischemia in one systematic review [5]. A wider variety of diseases affect the upper extremity arteries, and while atherosclerotic disease predominates as a cause of ischemia in the lower extremities, other etiologies are more common in the upper extremities [6-9] (table 1).

Arterial embolism — Thromboembolism is the most common cause of acute upper extremity ischemia responsible for 61 percent of cases, and typically affecting older patients (74 and 78 years in one review) [10,11]. The most common etiologies include atrial fibrillation (51 percent), valvular heart disease (6 percent), and isolated ischemic heart disease with left ventricular hypokinesis (4 percent) [12]. Other sources of cardioembolism include left atrial myxoma, left ventricular aneurysm, valvular vegetations in infective endocarditis, or nonbacterial marantic endocarditis.

Atherosclerosis of the ascending aorta or arch, innominate or subclavian arteries, or aneurysm affecting the subclavian, axillary (eg, poststenotic, chronic trauma from crutch use [13]), or ulnar artery (eg, hypothenar hammer syndrome [8]) can also be sources of embolism. (See "Thromboembolism from aortic plaque" and "Embolism from atherosclerotic plaque: Atheroembolism (cholesterol crystal embolism)" and "Embolism to the upper extremities".)

Paradoxical embolism to the upper extremities via a patent foramen ovale (PFO) from a site of deep venous thrombosis can also occur, though the incidence is unknown [14-16]. In a review that included 13 patients, all patients presented with simultaneous venous thromboembolism and PFO with a right-to-left shunt [14]. The upper extremity was affected in four patients.

Atherosclerotic plaque — Progressive atherosclerotic narrowing of subclavian, axillary, or brachial artery with resultant low flow, stasis, and eventual thrombosis is the mechanism for development of chronic ischemia. However, clinical manifestations of ischemia from acute native arterial thrombosis in a preexisting stenosis of an upper extremity artery is rare, presumably due to rich collateral network. It is reported in the form of case series only and is usually promoted by an underlying abnormality of the aortic arch [17], a lesion associated with arterial thoracic outlet syndrome [18], arterial catheterization or other vascular trauma, or a pre-existing stenotic atherosclerotic lesion [19].

De novo atherosclerotic arterial disease in the upper extremities is associated with known risk factors, particularly diabetes and renal failure, and with peripheral arterial disease (PAD) involving lower extremities [20]. Upper extremity vascular manifestations in patients with end-stage kidney disease overwhelmingly affect hand and digits. Symptomatic below-the-elbow atherosclerotic disease is rare. In one reported series, patients with symptomatic below-the-elbow atherosclerotic disease represented less than 1 percent of patients presenting with upper limb ischemia [21]. In this review, which included 108 patients, the average age was 59 years; 81 percent had diabetes and 41 percent had chronic kidney disease (not dialysis dependent). Most (93 percent) presented with digital ulceration and the remainder presented with hand pain. (See "Upper extremity atherosclerotic disease" and 'Hemodialysis access-induced distal ischemia' below.)

Traumatic injury — Penetrating or blunt injury to the upper extremity can injure the upper extremity arteries. Complex traumatic injuries that involve the soft tissues, arteries, nerves, and bony fractures account for the majority of upper extremity amputations [1].

Penetrating mechanisms can cause injury to any of the named vessels and may present with acute arm ischemia from thrombosis (picture 1A-B). Vascular injury can be direct or indirect. Direct injury from a knife or other implement, bullet or other projectile can cause partial or complete transection and thrombosis. Indirect injury results when the trajectory of a projectile is near an artery. The resulting blast effect can cause various degrees of intimal and medial injury that can also result in thrombosis. Traumatic upper extremity vascular injuries may also be associated with injury to the brachial plexus or individual upper extremity nerves from transection, blunt avulsion injury, or contusion from blast effect. (See "Severe upper extremity injury in the adult patient".)

Typical mechanisms resulting in upper extremity vascular injury from blunt trauma include the following:

●Subclavian artery thrombosis or avulsion is often due to severe traction injury on the shoulder that occurs from a direct blow, such as during a motorcycle crash when the victim is ejected and lands on the shoulder. These injuries often result in more devastating clinical consequences due to the associated avulsion of the brachial plexus from the cervical spinal roots or separation of the cords, resulting in an insensate and paralyzed upper extremity.

●Axillary artery injury can result from humeral dislocation or humeral neck fracture (image 1) [22].

●Brachial artery injury can result from mid-shaft humeral fracture (image 2 and picture 2) or supracondylar fracture. The brachial artery can also be stretched during elbow dislocation, resulting in thrombosis from intimal injury.

●Combined radial and ulnar artery injuries may occur from crush injury of the forearm. One example of such an injury is from a dog bite (picture 3), which can result in simultaneous crush of both vessels with thrombosis resulting in hand ischemia.

Thoracic endovascular aortic repair — Thoracic endovascular aortic repair (TEVAR) using currently approved devices may require coverage of the left subclavian artery in up to 40 percent of the cases. Subclavian artery coverage is generally well-tolerated due to excellent collateral circulation around the shoulder. Among patients who have had TEVAR with subclavian artery coverage without preemptive extra-anatomic revascularization, the risk of developing arm ischemia is overall low at about 6 percent [23]. Delayed arm ischemia can develop and usually presents with exertional arm pain. More serious symptoms, such as subclavian steal syndrome, ischemic rest pain, or tissue loss, are rare. (See "Endovascular repair of the thoracic aorta", section on 'Need for debranching procedures'.)

Arterial access complication — Arterial thrombosis or dissection related to arterial access for hemodynamic monitoring or from diagnostic or therapeutic arteriography may present with acute hand ischemia [24]. While rare, hand ischemia as a complication of radial artery access can be serious. A disproportionate severity of ischemia is often due to a combination of the direct arterial occlusion as well as the indirect peripheral vasoconstriction associated with the underlying cardiovascular instability for which the patient initially required invasive monitoring. (See "Access-related complications of percutaneous access for diagnostic or interventional procedures", section on 'Arterial thrombosis'.)

In the RadIal Versus femorAL access for coronary intervention (RIVAL) trial, radial access site complications were rare and only one patient was reported as having hand ischemia requiring surgery [25]. Other complications included hematoma in 1.2 percent and pseudoaneurysm needing closure in 0.2 percent.

Acute arterial dissection — Acute aortic dissection (type A aortic dissection) may present with upper extremity ischemia when the dissection extends into the great vessels. (See "Clinical features and diagnosis of acute aortic dissection", section on 'Pulse deficit'.)

Spontaneous subclavian or axillary artery dissections are rare and should alert the clinician to possible autoimmune etiology, such as Takayasu arteritis or giant cell arteritis (GCA).

Arterial thoracic outlet syndrome — Arterial thoracic outlet syndrome (aTOS), which is due to arterial compression most commonly related to a cervical rib, is the least common variant of thoracic outlet syndrome [18,26]. Symptomatic upper extremity ischemia related to aTOS is typically due to distal thromboembolism originating from the poststenotic aneurysm, rather than from progressive stenosis or thrombotic occlusion of a stenosis. When arterial occlusion does occur, the severity of limb ischemia is often blunted due to the collateral circulation around the shoulder. (See "Overview of thoracic outlet syndromes", section on 'Arterial TOS'.)

Aortitis/arteritis — Takayasu arteritis and GCA may also cause stenosis or occlusion of the subclavian or axillary arteries. (See "Overview of and approach to the vasculitides in adults" and "Clinical features and diagnosis of Takayasu arteritis" and "Clinical manifestations of giant cell arteritis".)

Takayasu arteritis is a "large vessel" vasculitis affecting the aorta and its branches typically affecting young females (<40 years old) and recognition requires a high index of suspicion since the clinical presentation in the early systemic inflammatory phase is often nonspecific. The presenting symptoms of either the acute systemic inflammatory phase or the "burnt out" or "occlusive" phase may overlap, but distinguishing between these phases is important for determining the treatment. The clinical presentation may include diminished pulses, differential blood pressures, and/or symptoms of upper extremity pain with exertion. Advanced symptoms such as ischemic rest pain and tissue loss are rare.

GCA is also systemic inflammatory disease generally affecting adults over age 50. GCA involves arteries of the head and neck, but it can also affect the aorta and rarely lower extremity vessels. The most common symptoms of GCA are throbbing headaches, scalp and temporal tenderness, jaw claudication, fever, and visual deficits. Early treatment is warranted to prevent serious complications such as blindness or stroke.

Radiation therapy — Radiation therapy to the neck or upper chest may result in accelerated atherosclerosis of the axillary or subclavian arteries [27]. The presentation is delayed, typically years later, and often affects the arterial beds that are largely spared from atherosclerosis [28,29].

Hemodialysis access-induced distal ischemia — Hemodialysis access-induced distal ischemia (HAIDI), also referred to as access-related hand ischemia (ARHI) or dialysis access–induced ischemic syndrome (DAIIS), presents as forearm or hand ischemia following creation of an arteriovenous (AV) access for hemodialysis. The incidence is about 3 percent. A thorough evaluation of the upper extremity vasculature is warranted in any patient dialysis patient using an AV access who develops ischemia.

Ischemic symptoms most commonly occur due vascular steal (ie, dialysis access steal syndrome [DASS]). Extremity symptoms range from mild (coolness, sensory abnormalities) to severe (ischemic rest pain, ulceration, gangrene). A small subset of the patients has only mild symptoms during hemodialysis but are otherwise asymptomatic. Most (up to 87 percent) patients experiencing symptoms of "steal" have an AV access that is brachial artery based [30]. Early diagnosis and immediate treatment are important for preventing progression to gangrene and limb loss. (See 'Digital gangrene' below and "Hemodialysis access-induced distal ischemia".)

More rarely, ischemia related to hemodialysis AV access presents as a variant known as ischemic monomelic neuropathy (IMN) with profound sensory and motor deficits in the hand. The presentation is almost immediate after the creation of the AV access and requires immediate treatment. IMN is more prevalent in the patients with diabetes and PAD. (See "Hemodialysis access-induced distal ischemia", section on 'Ischemic monomelic neuropathy' and "Hemodialysis access-induced distal ischemia", section on 'Differentiating IMN from DASS'.)

Severe PAD is an independent risk factor for hand ischemia after AV access surgery [31]. Prior to creating an AV access, proximal arterial occlusion should be ruled out. (See "Hemodialysis access-induced distal ischemia", section on 'Identifying correctable arterial lesions'.)

COVID-19-related upper extremity ischemia — COVID-19 secondary to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initially identified as an acute respiratory disease, but it was quickly recognized to involve multiple organ systems. Venous thromboembolism as well as arterial thrombosis have been reported. The hypercoagulability is thought to be multifactorial and incompletely understood and may be related to poor prognosis. (See "COVID-19: Hypercoagulability".)

In a review from three Dutch hospitals, the reported incidence of vascular thrombosis was 31 percent, with 27 percent due to venous thromboembolism and 3.7 percent due to arterial thrombosis [32]. The upper extremity is affected much less commonly compared with the lower extremity. There are few cases reported in the literature involving the upper extremities. It is interesting to note that arterial thrombotic events (77 percent) can present in patients with minimal or no respiratory symptoms [33]. Further studies are needed to understand the link between COVID-19 and arterial thrombosis. (See "COVID-19: Acute limb ischemia".)

Autoimmune disease/arteritis — Digital artery occlusion causing hand or finger ischemia is attributed to an autoimmune disease in up to 54 percent of the cases, although this patient population also has a high prevalence of smoking (68 percent) [34]. In a classic review, a comprehensive rheumatologic evaluation was obtained in the patients with digital ischemia due to small vessel disease. The arteritides identified included:

●Scleroderma/CREST syndrome (calcinosis cutis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) (See "Clinical manifestations and diagnosis of systemic sclerosis (scleroderma) in adults".)

●Mixed connective tissue disease (See "Mixed connective tissue disease".)

●Undifferentiated connective tissue disease (See "Undifferentiated systemic rheumatic (connective tissue) diseases and overlap syndromes".)

●Rheumatoid arteritis (See "Overview of the systemic and nonarticular manifestations of rheumatoid arthritis".)

●Systemic Lupus erythematosus (See "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults".)

●Sjögren disease (See "Clinical manifestations of Sjögren’s disease: Extraglandular disease".)

Scleroderma was the most common condition associated with small vessel disease in the hand. Thromboangiitis obliterans (Buerger disease), malignancy, and hypersensitivity angiitis with rapid-onset vascular occlusion were also observed. (See "Thromboangiitis obliterans (Buerger disease)".)

Most patients with autoimmune diseases with ischemic manifestations have secondary Raynaud phenomenon. (See "Clinical manifestations and diagnosis of Raynaud phenomenon", section on 'Clinical features' and "Treatment of Raynaud phenomenon: Refractory or progressive ischemia".)

Others — Other less common causes of upper extremity ischemia include the following:

●Accidental intra-arterial injection is often related to substance abuse disorder. In addition to the vascular consequences, soft tissue injury from drug extravasation can also occur. (See "Extravasation injury from cytotoxic and other noncytotoxic vesicants in adults".)

●Ergotism can lead to severe digital ischemia

●Case reports of unusual manifestations of hand ischemia from congenital AV malformations (eg, Parkes-Weber syndrome) have also been reported [35]. (See "Arteriovenous malformations of the extremities".)

●Ischemic lesions involving the upper extremity have also been reported in association with hypercoagulable states (eg, heparin-induced thrombocytopenia, malignancy, disseminated intravascular coagulation, coronavirus disease 2019 [COVID-19] [36,37]). Digital ischemia and necrosis due to small vessel thrombosis, referred to as acral vascular syndrome, is a relatively rare presentation. A neoplastic origin should be considered, particularly in older patients with a new onset acral vascular syndrome and without any known cardiovascular causative factors. The paraneoplastic acral vascular presentation may range from Raynaud phenomenon to acrocyanosis to tissue necrosis (gangrene) [38,39].

CLINICAL PRESENTATION — The clinical presentation depends on the onset of the disease.

Acute ischemia — Acute limb ischemia is defined as a sudden decrease in limb perfusion with the onset of symptoms of less than two weeks duration. The clinical presentation depends on the time course of vessel occlusion, the location of the affected vessels, and the ability to recruit collateral channels to provide flow around the occlusion, and whether there is underlying vascular disease. The classic physical signs of acute limb ischemia in a patient without underlying occlusive vascular disease are the six Ps (pain, pallor, pulselessness, poikilothermia, paresthesia, and paralysis). When collateral circulation cannot compensate, minor sensory deficits develop as a sign of early nerve dysfunction; major sensory or motor loss is indicative of advanced ischemia.

Limb symptoms — Acute upper limb ischemia typically presents with sudden onset of a cool, pulseless, and painful upper extremity. In the upper extremity, these findings usually suggest acute embolism from a cardiac source. In a review of patients who underwent embolectomy, all patients presented with unilateral coldness of the upper extremity without radial pulse and with a "water-hammer" pulse at the arterial level where the embolus was lodged [12]. Associated findings included at least one of the following: ischemic rest pain (52 percent), paresthesias (30 percent), or some degrees of paralysis (26 percent).

The extent of limb involvement depends on the location of arterial occlusion. As an example, an embolus typically lodges at a proximal branch point where the vessel narrows, such as the take-off of the profunda brachii leading to entire limb ischemia, or the branching of the brachial artery in the antecubital fossa leading to forearm ischemia.

Isolated hand symptoms — With small vessel disease, often caused by autoimmune diseases and arteritides. ischemic symptoms (coolness, pain) are limited to the hand. In a review of specifically hand ischemia, the pathophysiologic mechanism responsible was emboli in 6 percent, vasospasm in 10 percent, thrombosis or "sludging" in 28 percent, occlusive disease in 26 percent, and occlusive disease associated with vasospasm or external compression in 30 percent [40]. (See 'Autoimmune disease/arteritis' above.)

Chronic ischemia — Chronic ischemia (>2 weeks after onset of symptoms) affecting the upper extremity has a varied presentation depending on the location and underlying etiology.

Chronic proximal occlusions can be asymptomatic or present with history of exertional arm symptoms and/or signs and symptoms of "subclavian steal" syndrome. Chronic proximal arterial occlusions are often well-tolerated due to excellent collateral network. This is typically provided via a retrograde flow in the vertebral arteries through the complete circle of Willis. In addition, the basal metabolic needs of the upper extremities are relatively lower compared with the lower extremity. The only clinical indicator of vascular disease in this large number of asymptomatic patients is a difference between the arm blood pressures. It would not be surprising to see a 30 to 40 mmHg difference with proximal subclavian artery occlusion. Therefore, vascular examination is important to measure the blood pressure in both arms. (See "Upper extremity atherosclerotic disease", section on 'Presentations'.)

A more dramatic presentation is the "subclavian steal" syndrome (figure 21), which is pathognomonic of the proximal subclavian artery occlusion. Classic symptoms of vertebrobasilar insufficiency may include dizziness and near syncope to complete syncopal attacks associated with use of the ipsilateral upper extremity. The patient may have weakly palpable ipsilateral radial and ulnar pulses, which will obliterate during isometric exercise. (See "Subclavian steal syndrome", section on 'Introduction'.)

More distal arterial occlusions are sometimes difficult to identify based on history and physical exam alone. Also, isolated single vessel occlusions may go unnoticed or remain subclinical due to adequate collateral circulation [4].

Digital gangrene — Digital gangrene is the presentation of small vessel occlusions in the hand from atheroembolism (atherosclerotic debris), thromboembolism (aneurysmal disease), or arteritides (picture 4). Digital gangrene from proximal arterial occlusion (atherosclerotic occlusion) is rare [41]. Dialysis access steal syndrome in hemodialysis patients using an arteriovenous access can progress to digital gangrene if not recognized and treated in a timely fashion.

PHYSICAL EXAMINATION — A careful examination of both upper extremities is necessary to detect signs of acute or chronic ischemia and includes the following:

●Pulse examination

●Bilateral upper extremity blood pressures

●Evaluation of capillary refill

●Neurologic examination assessing sensation and muscle strength

●Clinical signs of "steal" syndrome

The quality and character of the peripheral pulses in the affected extremity, as well as the contralateral extremity, are evaluated and compared. The vascular examination should include palpation of all pulses, including the subclavian, axillary, brachial, radial, and ulnar arteries, as well as the lower extremity pulses (ie, femoral, popliteal, dorsalis pedis, and posterior tibial pulses). Since the quality of the pulse examination can vary, a handheld Doppler should be used to confirm the presence of distal pulses (eg, radial artery, ulnar artery Doppler signals). The operator should listen for arterial and venous signals (table 2). If Doppler signals are present, the wrist-brachial index (WBI) should be obtained. The manner of obtaining the WBI and interpretation is discussed separately. In general, the absence of any distal Doppler signals (arterial and venous) indicates severe ischemia. For the upper extremity, although the WBI may vary significantly depending upon the location of the thrombus or embolus, a value <0.4 is indicative of severe ischemia. (See "Noninvasive diagnosis of upper and lower extremity arterial disease", section on 'Wrist-brachial index'.)

Six Ps of acute ischemia — The six Ps of acute ischemia include pain, pallor, poikilothermia, pulselessness, paresthesia, and paralysis.

●Pain – Pain associated with acute arterial occlusion is usually located distally in the extremity, gradually increases in severity, and progresses proximally with increased duration of ischemia. Later, the pain may decrease in severity due to progressive ischemic sensory loss.

●Skin perfusion – The skin of both the normal and affected extremity should be examined for temperature, color, and capillary refill. The skin of the ischemic extremity is typically cool (Poikilothermic) and Pale or mottled with delayed capillary filling. Blistering of the skin is an ominous sign of advanced ischemia. Both extremities should also be examined for signs of chronic ischemia suggesting a possible systemic condition.

●Pulses – Acute limb ischemia typically manifests with severely reduced pulses.

●Neurologic examination – Subjective sensory deficits such as numbness or Paresthesias are signs of early nerve dysfunction secondary to ischemia. Major loss of sensory or motor function (Paralysis) is indicative of advanced ischemia.

DIAGNOSIS — A clinical diagnosis of upper extremity ischemia can be made based solely on history and physical examination in about 90 percent of patients. The patient's presenting clinical features, and importantly history (eg, arrhythmia, valvular heart disease, trauma, prior access, history of radiation, recent dialysis access), often point to a likely etiology for upper extremity ischemia. (See 'Incidence and etiologies' above.)

Asymmetry in the vascular examination is highly suggestive of a surgically correctable etiology. As examples, sudden unilateral limb ischemia with normal pulses in the contralateral extremity suggest the absence of chronic arterial disease and that an embolus is the likely etiology of the acute ischemia. An acute onset left upper extremity ischemia in a patient with chest pain and hypertension suggests aortic dissection. By contrast, symmetrically reduced pulses in both the upper extremity and lower extremities suggests a systemic etiology.

Clinical classifications

Severity of acute ischemia — Acute ischemia, which is defined as a sudden decrease in limb perfusion in patients who present within two weeks of the primary event, is classified using the Society for Vascular Surgery (SVS)/International Society for Cardiovascular Surgery (ISCVS) (Rutherford) classification based on clinical findings including degree of pain, vascular examination and Doppler findings, and presence and degree of sensorimotor deficits (table 2). (See "Classification of acute and chronic lower extremity ischemia", section on 'Acute extremity ischemia'.)

Severity of chronic ischemia — While chronic symptoms from proximal atherosclerotic lesions are uncommon given the collateral circulation, when symptoms do occur, the severity of chronic ischemia can be classified in a manner analogous to chronic ischemia affecting the lower extremity. (See "Classification of acute and chronic lower extremity ischemia", section on 'Rutherford'.)

Vascular imaging — While a clinical diagnosis of upper extremity ischemia can generally be established based on history and physical examination alone, vascular imaging or other studies are often needed to establish the location, severity, and extent of vascular disease.

Acute ischemia — The type of vascular imaging chosen for acute upper extremity ischemia weighs the availability of a specific imaging modality and the time required to perform and interpret the study against the urgency and possible methods of revascularization (eg, endovascular, open surgery). Patients with an immediately threatened extremity should preferentially undergo further evaluation in association with any planned intervention (endovascular, open surgical).

Patients with viable or marginally threatened limbs are usually candidates for urgent vascular imaging (typically computed tomographic [CT] angiography, or catheter-based arteriography) to evaluate arterial anatomy and to potentially institute thrombolytic therapy. The limitations of the CT angiography include artifact from heavy arterial calcification or from metallic foreign bodies such as bullet fragments in the case of traumatic injury. Software is available that can help to reduce the artifact from the foreign bodies. While CT and magnetic resonance (MR) angiography can reliably diagnose the location and severity of arterial stenosis or occlusion with high sensitivity and specificity, other modalities are needed for treatment (eg, thrombolysis, angioplasty). Catheter-based arteriography (digital subtraction arteriography) generally provides the most useful information and a treatment option. In addition to demonstrating arterial anatomy, arteriography can usually distinguish between thrombosis and embolism.

●An embolus will often demonstrate a sharp cutoff with a rounded reverse meniscus sign. The embolus may also be visible as an intraluminal filling defect if the vessel is not completely occluded. Other findings that are most consistent with an embolus include the presence of otherwise normal vessels, the absence of collateral circulation, and the presence of multiple filling defects.

●Arterial thrombosis is usually seen as a sharp or tapered, but not rounded, cutoff on arteriography. For patients with thrombosis of an atherosclerotic segment, or occlusion of a prior revascularization, vascular imaging studies should be compared with any previously performed studies (if available).

These clinical and radiographic features help determine whether surgical revascularization or catheter-directed thrombolysis (with or without endovascular intervention) is the most appropriate initial treatment. When thrombolysis is more suitable, proceeding directly to catheter-based arteriography expedites treatment and minimizes overall intravenous contrast load.

Chronic ischemia — For chronic ischemia, vascular imaging may include duplex ultrasound, CT or MR angiography, or conventional catheter-based arteriography. The type of vascular imaging selected depends on the likely cause of ischemia. Noninvasive vascular studies (eg, digital plethysmography, formal wrist-brachial indices and pulse volume recordings) are frequently performed initially to confirm the diagnosis and level of disease. Cerebrovascular duplex ultrasonography may show retrograde vertebral arterial Doppler waveforms, which signify proximal subclavian artery occlusion (image 3 and image 4) and may demonstrate typical "steal" physiology. Noninvasive vascular studies are also useful for long-term surveillance after revascularization.

For patients with hemodialysis arteriovenous access and symptoms of ischemia, dialysis access steal syndrome can be confirmed with "normalization" of duplex flow or digital plethysmography waveforms with manual occlusion of the AV fistula. Digital subtraction angiography can be used to evaluate the vasculature to rule out preexisting stenotic lesions that limit flow into the forearm and hand. It also helps evaluate the quality of the outflow vessels. (See "Hemodialysis access-induced distal ischemia", section on 'Diagnosis'.)

Other evaluation — For patients with embolism, further evaluation and treatment focus on preventing recurrent events. Following an embolic event, after managing the acute ischemic insult, 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 the use of adjunctive medical therapies. (See "Thromboembolism from aortic plaque", section on 'Treatment' and "Embolism to the upper extremities", section on 'Prevention of future embolic events'.)

DIFFERENTIAL DIAGNOSIS

●A cerebrovascular event can present with upper extremity symptoms (eg, paresthesias, motor weakness) that mimic early symptoms of acute upper limb ischemia. A thorough cardiovascular and neurologic examination should help make the distinction. (See "Overview of the evaluation of stroke".)

●Acute compartment syndrome of the upper extremity is commonly related to traumatic injury. It may be difficult to differentiate hand ischemia that is due to arterial injury from that which is related to increased compartment pressure (arm, forearm, hand). Important clinical findings of compartment syndrome include severe pain disproportionate to the physical findings, passive extension causing pain of the compartment constituent muscles, or tense fascia by palpation. If not recognized, compartment syndrome can progress to an irreversible state (ie, Volkmann contracture). (See "Pathophysiology, classification, and causes of acute extremity compartment syndrome" and "Acute compartment syndrome of the extremities" and "Upper extremity fasciotomy techniques".)

●Complex regional pain syndrome is a disorder that usually affects the distal limbs and is characterized by pain, swelling, limited range of motion, vasomotor instability, skin changes, and patchy bone demineralization. It frequently begins following a fracture, soft tissue injury, or surgery. Symptoms may be confused with chronic distal ischemia; however, the pulses are normal. (See "Complex regional pain syndrome in adults: Pathogenesis, clinical manifestations, and diagnosis".)

●Frostbite, which can lead to digital gangrene, is a severe, localized cold-induced injury due to freezing of tissue. History of an antecedent exposure usually makes the diagnosis. However, it is important to note that certain populations with underlying conditions predisposing to upper extremity ischemia can experience exaggerated responses to cold stimuli. (See "Accidental hypothermia in adults" and "Frostbite: Emergency care and prevention".)

●Phlegmasia cerulea dolens due to extensive deep venous thrombosis of the proximal veins in the upper extremity is very rare and the diagnosis requires a high index of suspicion [42]. The risk of upper extremity limb loss is exceedingly rare, and every observed case is worthy of being reported in the literature. Concurrent lower extremity phlegmasia cerulea dolens is an independent marker for upper extremity disease. (See "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Phlegmasia cerulea dolens'.)

●Other etiologies that cause isolated hand or finger pain, or motor or sensory abnormalities (eg, injury, infection, hematoma) may be confused with hand/digital ischemia. These are reviewed separately. (See "History and examination of the adult with hand pain" and "Overview of hand infections".)

APPROACH TO TREATMENT — Treatment is based on the etiology, severity, and duration of upper extremity ischemia. Among all arterial procedures, those performed in the upper extremity account for approximately 4 percent [43].

Treatment by clinical classification — The Society for Vascular Surgery (SVS)/International Society for Cardiovascular Surgery (ISCVS) (Rutherford) classification (table 2) stratifies limb ischemia based on clinical findings and informs treatment. (See 'Severity of acute ischemia' above.)

●Class I ischemia represents a viable extremity that requires urgent evaluation.

●Class II ischemia represents a marginally (IIa) or immediately threatened (IIb) extremity that is salvageable if treated with urgent (IIa) or emergency (IIb) revascularization.

●Class III ischemia represents irreversible ischemia with nonviable, unsalvageable extremity requiring amputation.

For patients with a viable extremity awaiting definitive management, most patients are initially treated with intravenous unfractionated heparin as soon as the diagnosis of acute upper extremity ischemia is made to limit propagation of thrombus. Depending on the etiology of ischemia, longer-term antithrombotic therapy may be indicated.

For patients with atherosclerotic disease, optimal medical therapy is important for reducing the patient's risk for future cardiovascular events, which includes antiplatelet therapy, lipid lowering, and blood pressure control. (See "Upper extremity atherosclerotic disease", section on 'Management'.)

When revascularization is indicated, important factors that impact the timing and method of revascularization (open surgical endovascular), are listed below. Techniques for upper extremity revascularization are reviewed separately. (See "Surgical and endovascular techniques for aortic arch branch and upper extremity revascularization".)

●Presumed etiology (embolus versus thrombus)

●Lesion location and length

●Duration of symptoms

●Availability of autologous vein for bypass grafting

●Suitability of the patient for surgery or intervention

Treatment by etiology — Specific treatment is discussed in separate topic reviews.

●(See "Embolism to the upper extremities", section on 'Approach to limb management'.)

●(See "Upper extremity atherosclerotic disease", section on 'Management' and "Subclavian steal syndrome", section on 'Management'.)

●(See "Surgical management of severe upper extremity injury" and "Surgical reconstruction of the upper extremity".)

●(See "Endovascular repair of the thoracic aorta", section on 'Need for debranching procedures' and "Endovascular repair of the thoracic aorta", section on 'Extremity ischemia'.)

●(See "Hemodialysis access-induced distal ischemia", section on 'Treatment options'.)

●(See "Overview of thoracic outlet syndromes", section on 'Thoracic outlet decompression'.)

●(See "Treatment of Raynaud phenomenon: Initial management" and "Treatment of Raynaud phenomenon: Refractory or progressive ischemia".)

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" and "Society guideline links: Extremity compartment syndrome" and "Society guideline links: Severe blunt or penetrating extremity trauma".)

SUMMARY AND RECOMMENDATIONS

●Upper extremity ischemia – Upper extremity ischemia is relatively rare compared with the ischemia affecting the lower extremity. Upper extremity ischemia can be due to a sudden (ie, acute) or gradual (ie, chronic) loss of blood flow. Acute ischemia is defined as having an onset of symptoms of less than two weeks. Acute thrombosis of an already narrowed segment is much less common in the upper extremity, but it can also occur (ie, acute-on-chronic ischemia). (See 'Introduction' above.)

●Etiologies of ischemia – The upper extremity arterial circulation is affected by a wide variety of diseases (table 1), which contrasts with the lower extremities, for which atherosclerotic occlusion predominates. The most common cause of acute upper extremity ischemia is embolism from a cardiac source. Acute arterial occlusion can also be due to thrombosis (eg, atherosclerotic stenosis) or related to direct arterial trauma, arterial dissection, or acute thrombosis of a stent or graft. Upper extremity ischemia related to hemodialysis arteriovenous (AV) access can present as dialysis access steal syndrome (DASS) or ischemic monomelic neuropathy (IMN), and when it occurs, it is a major source of upper extremity morbidity. (See 'Incidence and etiologies' above.)

●Clinical presentations – The clinical presentation of acute arterial occlusion depends upon the time course of vessel occlusion, the location of the affected vessels, and the ability to recruit collateral channels to provide flow around the occlusion, and whether there is underlying vascular disease. Given the robust collateral circulation in the upper extremity (around shoulder, around elbow), clinical signs can vary depending on the location of the lesion.

•Acute ischemia – The classic physical signs of acute limb ischemia in a patient without underlying occlusive vascular disease are the six Ps (pain, pallor, pulselessness, poikilothermia, paresthesia, and paralysis). In the upper extremity, these findings usually suggest acute embolism from a cardiac source. When collateral circulation cannot compensate, subjective sensory deficits are signs of early nerve dysfunction, and major sensory or motor loss is indicative of advanced ischemia. (See 'Acute ischemia' above and 'Physical examination' above.)

•Chronic ischemia – is uncommon in the upper extremities compared with the lower extremities because of the robust collateral circulation and the relatively lower basal metabolic needs of the upper extremities. (See 'Chronic ischemia' above.)

●Clinical classification – A complete examination of the extremity and full vascular examination is performed and should document the classification of ischemia (table 2) to assist in determining the need for and urgency of treatment. (See 'Clinical classifications' above and 'Approach to treatment' above.)

•Viable limbs are under no immediate threat of tissue loss but should be evaluated expediently.

•Marginally threatened limbs are salvageable with urgent revascularization.

•Immediately threatened limbs are salvageable with emergency revascularization.

•Limbs with irreversible ischemia will require amputation regardless of any therapy that is instituted.

●Vascular imaging – While the diagnosis of upper extremity ischemia can usually be made based on clinical findings, vascular imaging may be necessary to identify the specific etiology. Patients with an immediately threatened extremity treatment should preferentially undergo further evaluation in association with any planned intervention (endovascular, open surgical). Patients with viable or marginally threatened limbs are usually candidates for urgent vascular imaging (computed tomographic [CT] angiography, catheter-based arteriography) to evaluate arterial anatomy. When thrombolysis is suitable, proceeding directly to catheter-based arteriography expedites treatment and minimizes overall intravenous contrast load. (See 'Vascular imaging' above.)

●Treatment – Treatment is based on the etiology, severity, and duration of upper extremity ischemia. Most patients are initially treated with intravenous unfractionated heparin as soon as the diagnosis of acute upper extremity ischemia is made to limit propagation of thrombus. Specific treatment depends on the severity and etiology of ischemia and may include watchful waiting, thrombolytic therapy, upper extremity revascularization, and for some etiologies, adjunctive evaluation and treatment to prevent recurrent ischemia. (See 'Approach to treatment' above and 'Other evaluation' above.)