Acute arterial occlusion is one of the most devastating diseases in vascular surgery, resulting in limb loss, long-term morbidity, and death. Early recognition of symptoms of limb ischemia is necessary in order to salvage limb function and prevent an increased risk of mortality. Patients with acute limb ischemia often present soon after the onset of symptoms and are able to describe the exact moment symptoms began. This process should be differentiated from chronic limb ischemia, which occurs over a prolonged period of time with progression of symptoms. Severity of symptoms is dependent on the amount of arterial collateralization around the site of occlusion which can often reflect underlying chronic vascular disease.

The aim of this chapter is to discuss the diagnosis, etiology, pathophysiology, and treatment of patients with acute limb ischemia.

Pathophysiology

Acute arterial ischemia occurs as a result of embolization, thrombosis, trauma, or vasculitis (Figures 36-1 and 36-2). A central source can be found in the vast majority of patients with macroembolic disease (Table 36-1). These patients are likely to have atrial arrhythmias or recent myocardial infarction. The presentation of embolization is sometimes difficult to distinguish from thrombosis. Patients with arterial emboli typically have a discrete onset of symptoms, have a history of or are at risk of emboli, have no history of claudication, and have preserved flow in the contralateral extremity. In contrast, patients with arterial thrombosis are more likely to have preexisting vascular disease and a history of claudication and physical findings of disseminated disease or previous extremity bypass (Table 36-2).

Factors affecting the clinical outcome of embolic disease include the size of the affected vessel, the amount of collateral flow, and the degree of obstruction. In patients with underlying atherosclerotic vascular disease, an embolus may have little clinical significance because of preexisting collaterals. However, embolization to a healthy artery will create significant ischemia because of lack of collateralization. Once embolization occurs, events that follow must be abrogated to prevent irreversible ischemia. Clot propagation occurs once emboli lodge within the affected vessel and an environment of stasis develops allowing further clot formation and propagation. Limb ischemia may be made worse by distal migration of clot fragments and debris. Venous thrombosis may occur because of the low flow state created by the embolus and resultant ischemia. This phenomenon is clinically significant in that it may make revascularization more difficult, increase the patient’s risk for pulmonary emboli, and may result in compartment syndrome after revascularization.

Regardless of the causes, the ischemia resulting from arterial occlusion follows a relatively similar course. The extremities are more resistant to ischemia than other tissues and can tolerate up to 5 to 6 hours of ischemia depending on the amount of collateralization. Each of the tissues within the extremity has different vulnerabilities. Nerves are the most sensitive, resulting in paresthesia as an early sign of ischemia, while skin and bone are the most resistant. Paresis and paralysis represent severe and limb-threatening ischemia. Skeletal muscle comprises the largest and most metabolically active constituent of the lower extremity. As such, skeletal muscle plays a significant role in the morbidity and mortality of acute limb ischemia and resulting reperfusion injury. The lactic acidosis, hyperkalemia, and myoglobulinuria, which occurs when ischemic muscle is reperfused, can result in systemic dysfunction and renal failure.

Cellular membrane function is impaired by severe ischemia from direct membrane damage as well as damage to the membrane transport proteins, including adenosine triphosphatase (ATPase). This results in a loss of normal cellular barriers and transport with resulting intracellular edema. Interstitial edema occurs secondary to increased basement membrane permeability to ions and proteins. The amount of interstitial edema depends on the length of ischemia; as length of ischemia increases, interstitial edema increases, especially in patients without adequate collateralization. The effects of interstitial edema are most evident in fascial compartments after revascularization. As interstitial edema increases, compartment pressures increase beyond capillary perfusion pressures, usually around 30 mm Hg and compartment syndrome develops. In the setting of compartment syndrome, fasciotomy must be performed in addition to revascularization to allow for adequate tissue perfusion.

As ischemia develops, the sarcolemma plasma membrane becomes disrupted, resulting in intracellular swelling. Once flow is reestablished, the damaged sarcolemma membrane cannot maintain a normal cellular barrier. Intracellular ions, proteins, and enzymes are released into the circulation, resulting in the myonephropathic or reperfusion syndrome. Myoglobin, once released systemically, is cleared by the kidney. As myoglobin casts deposit in the renal tubules, acute renal failure may ensue. Myoglobin and creatinine phosphokinase levels can be elevated for up to 4 days following reperfusion. Also, hyperkalemia, from release of intracellular potassium stores, can cause myocardial depression and dysrhythmias.

In addition to systemic effects of ischemia and reperfusion, there are numerous events that occur at the tissue level, which are incompletely understood. As ischemia develops, cellular oxygen delivery becomes hampered, normal cellular ionization becomes disrupted, and cellular membrane permeability increases, as described above. With reperfusion, injury can continue to occur at the cellular level, despite adequate oxygen delivery. As oxygen delivery returns to the tissues, neutrophils within damaged tissue take up oxygen, converting the molecule via univalent reduction into free radical species, including superoxide radicals, hydrogen peroxide, and hydroxyl radicals. Free radicals are typically generated through an nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme located on the cellular membranes of neutrophils. Once formed, these compounds are highly unstable, usually overwhelm the body’s natural scavenging system, and begin to attack the phospholipid cellular membrane, primarily through reduction of fatty acids, resulting in continued cellular damage.¹

Diagnosis

In light of the potentially life-threatening effects of untreated ischemia, early diagnosis of acute limb ischemia is important. The diagnosis of acute limb ischemia is usually a clinical one, made by history and physical examination. It is important when obtaining the history of extremity pain to include duration of symptoms, intensity, and location. In general, patients with acute arterial occlusion from embolic sources present soon after onset of symptoms with complaints of severe lower extremity pain and can document a discrete onset. The past history should include prior vascular surgeries, cardiac history (myocardial infarction or arrhythmias), history of claudication, history of coagulation disorders, and known aortic aneurysms. Risk factors for atherosclerotic disease should be ascertained as well, including diabetes, hypertension, hyperlipidemia, and smoking history.

Physical examination can often localize the point of arterial occlusion. The classic mnemonic for arterial occlusion is the “six Ps”: pain, pulselessness, pallor, paralysis, paresthesia, and poikilothermia. The affected limb, as well as contralateral extremity, should be examined for pulses. The affected extremity may be pale and cool. Patients complain of a constant pain or pain with simple passive movement. As ischemia progresses, the patient may develop numbness or neuromuscular dysfunction, foot drop, indicating damage to nerves and muscles. As a rule, patients with “two Ps,” paralysis and paresthesia, require immediate intervention to prevent limb loss.

The Rutherford classification system has been developed to define the extent of ischemia.^2,3 The system is divided into three classes:

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  Class 1: a viable extremity that has no ischemic pain and no neurologic deficits, is with clearly audible Doppler flow, and does not require intervention.

  
  
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  Class 2a: limbs that are threatened to have mild neurologic deficits and ischemic pain with no clear Doppler flow but do not require immediate intervention.

  
  
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  Class 2b: limbs that are threatened and require immediate intervention.

  
  
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  Class 3: limbs with irreversible ischemia, profound motor and sensory loss, absent capillary flow, and skin marbling; these limbs are not salvageable.

Distal embolization can be difficult to distinguish from in situ thrombosis, particularly in the setting of underlying vascular disease. Patients presenting with limb ischemia who do not have paralysis or paresthesia may, as time allows, undergo echocardiography, electrocardiography, cardiac assays, and thrombophilia workup to evaluate for possible embolic sources. Imaging modalities have been developed and refined to help determine the cause of acute limb ischemia.

The standard for identifying arterial occlusion remains contrast arteriography. It allows for accurate diagnosis and operative planning. Angiography can help differentiate an embolus from in situ thrombosis. On arteriogram, emboli appear as a filling defect with a meniscus sign in an otherwise normal vessel. In addition, patients with embolization typically have sparse collateral flow without the presence of other arterial disease. Finally, a vessel with multiple filling defects should raise the suspicion of embolization. In acute in situ thrombosis, patients will typically have multilevel atheromatous changes and diffuse collaterals. From a therapeutic standpoint, arteriography offers an opportunity for thrombolytic therapy and endovascular approaches for treating ischemia. However, arteriography is not without risks, including contrast nephrotoxicity, and antiphylaxis and should be reserved for patients for whom a surgical intervention is planned.

Noninvasive modalities as an alternative to arteriography include duplex ultrasound, Magnetic resonance (MR) angiography, and computed tomography (CT) scan angiography. Duplex ultrasound has been shown to be quite useful in evaluating the patency of bypass grafts and single arterial segments, but it has not proven as effective as arteriography in planning for operative intervention. MR angiography is gaining popularity in some centers, as its sensitivity and specificity are greater than duplex ultrasonography and the risks of contrast nephropathy are significantly reduced through the use of gadolinium as a contrast agent. MR is useful for identifying possible bypass targets in the distal extremity. CT scan angiography with 3D reconstruction has also become a popular noninvasive imaging modality, with sensitivity and specificity rivaling MR angiography. It is associated with a large contrast load.⁴ Despite imaging advances, for those patients in whom therapeutic interventions are planned, or in patients when the delay of intervention may have adverse consequences, contrast arteriography remains the standard of care.

Whenever embolic or thrombotic events occur, thrombophilia must be considered as an etiology, or at least a contributing factor (Table 36-3). Up to 15% of the population may have an acquired or genetic propensity to clot. In addition to the disorders listed in the table, in patients who have been previously treated for cardiovascular disease, new onset of embolic or thrombotic events may be a harbinger of heparin-associated antibodies or thrombosis. Thrombolytic disorders should be considered and treated in conjunction with relieving the ischemia presented. Antithrombin III deficiency should be suspected in patients who require large doses of heparin. In general, a family history of thrombotic events can raise a suspicion for hereditary genetic disorders.

Arterial thromboembolism has long been a problematic disease in vascular surgery. Prior to the existence of catheter-based interventions and synthetic grafts, removing embolic material was difficult. The landmark introduction of the Fogarty catheter, a balloon embolectomy device, allowed for easy arterial access and retrieval of embolic material without significant damage to the native vessel. Since that time many changes have occurred in the treatment of acute arterial thromboembolism. The introduction of thrombolytic agents and newer minimally invasive techniques has significantly changed the field of vascular surgery. Despite these advances, mortality rates from acute peripheral arterial occlusion have changed only slightly, averaging 10% to 25%.⁵ Medical comorbidities and concurrent chronic vascular disease have kept the morbidity and mortality constant, even in light of technological advances. Part of the difficulty in the treatment of peripheral thromboembolism is the change in etiology from previous decades. Prior to the advent of antibiotics, rheumatic heart disease, and peripheral embolization from mitral valve vegetations were the most common causes for thromboembolic phenomena. Today a plethora of etiologies exist, including atherosclerotic heart and vascular disease, dysrhythmias, and iatrogenic catheter manipulation.⁶

Arterial emboli are classified on the basis of size, origin, and content. This classification allows for a uniform treatment and understanding of the natural history of embolic phenomena. For the purposes of discussion, we will divide emboli into macro- and microemboli. These are clearly two separate entities with different clinical presentations and treatment options.