TOPIC: Classification of acute extremities ischemia. Clinical stages. Diagnosis. Differencial diagnosis. Methods of surgical treatment.
Acute Arterial Obstruction
The manifestations of acute arterial occlusion vary greatly, depending on the level and severity of the obstruction, timing from onset to presentation, and degree of chronic vascular disease and collateral circulation. The classic signs and symptoms of acute arterial occlusion include pain, pallor, pulselessness, paresthesias, and paralysis. Cutaneous manifestations are among the earliest in an acute occlusion. Pallor is seen initially and occurs with the loss of pulses. If timely revascularization does not take place, blistering of the skin may develop, followed by frank gangrene. Sensorimotor manifestations are among the most common symptoms in acute ischemia. Pain is noted early in the course of events; however, this may progress to numbness, which should not be mistaken as improvement. As ischemia progresses, nerve dysfunction may lead to sensory loss, followed by paralysis and muscle destruction resulting in paralysis; a late manifestation of ischemia in muscle is rigor, suggesting muscle death. The quality of pulses in the contralateral extremity can be very informative. It is uncommon for a patient with chronic vascular disease in one extremity to have full, strong, distal pulses in the other. A normal pulse exam in the contralateral leg suggests that the patient has had an acute event in the absence of chronic disease. This patient is unlikely to have developed significant collaterals, and expediency in obtaining revascularization is vital. The two major causes of acute arterial occlusion are emboli and thrombosis. An embolic source accounts for 80% of cases. The most common sites in the lower extremity for emboli to become lodged are, in descending order, the femoral, iliac, aorta, and popliteal arteries. Acute thrombosis, usually of a previously stenotic area in the setting of atherosclerosis, is the second most common cause of acute arterial occlusion. Thrombosis may also occur in the setting of low flow states such as congestive heart failure or hypotension, in hypercoagulable states, and in vascular grafts. The management of the patient with acute lowerextremity ischemia includes a thorough but expeditious history and physical, followed by optimization of hemodynamics and fluid balance. Unless a contraindication exists, most patients are heparinized. If the patient is thought to have potentially viable extremities, the lesion can be further delineated with arteriography. At this point a decision is made whether to treat the patient operatively or with an attempt at thrombolysis. If open surgery is chosen, the most common procedure is a catheter embolectomy, usually via a cutdown at the femoral or belowknee popliteal location. Alternatively, particularly in the setting of a thrombosed bypass graft, bypass reconstruction may be necessary. In an analysis of multiple series, the mortality and limb salvage rates were 12.6% and 78%, respectively, for the use of heparin alone in the setting of acute ischemia, 17% and 84% for thromboembolectomy alone, and 10.2% and 92% when the combination of perioperative heparin and catheter embolectomy was used.30 Postoperatively one should consider long-term anticoagulation as it may reduce the incidence of recurrent embolization from 21% to 7%.30 The comparison of lytic therapy and surgical therapy in the initial management of acute lower-extremity ischemia has been carefully studied in several multiinstitutional studies. In one study there was a significantly increased number of major adverse events in the thrombolysis group at 1 month as compared to the surgery-alone group. However, when patients were stratified to duration of ischemia, there were clear trends in favor of lysis in patients whose onset of ischemic symptoms was less than 14 days before presentation.31 An optimal situation in the setting of acute ischemia would be that of a patient with evidence of an acute thrombotic event who undergoes thrombolysis that clears the thrombus and reestablishes flow nonoperatively and also uncovers a culpable lesion which would be angioplastied or surgically reconstructed electively. Other principles of management of the patient with acute lower-extremity ischemia include careful monitoring postoperatively for metabolic derangements related to reperfusion such as acidosis and hyperkalemia, evaluation of the urine for myoglobin, and, if present, treatment with hydration, manitol, and bicarbonate to induce an alkaline diuresis. Additionally, if a limb has been ischemic for a significant time or develops elevated compartment pressures, one should have a low threshold for performing fasciotomy. Embolic events can also take the form of atheroemboli as atherosclerotic debris in a proximal artery dislodges and occludes distal arteries. The most common manifestation of this event is the blue toe syndrome. Blue toe syndrome consists of the sudden appearance of a cool, painful, cyanotic toe or forefoot in the often perplexing presence of strong pedal pulses and a warm foot. By far the most common source is the distal aorta, but atheromatous debris can embolize from anywhere along the aorta as well as from peripheral arteries such as the femoral or popliteal. These episodes portend both similar and more severe episodes in the future. Therefore, location and eradication of the embolic source is usually indicated.32
Section XI - ACUTE LIMB ISCHEMIA
Kenneth Ouriel, MD
Chapter 66 - Acute Limb Ischemia
KARTHIKESHWAR KASIRAJAN, MD, FACS KENNETH OURIEL, MD, FACS, FACC
Limb ischemia occurs when an extremity is deprived of adequate blood flow. Symptoms depend on the severity of hypoperfusion. The process can develop suddenly and, when the patient presents soon after its onset, the entity is said to represent acute limb ischemia. Acute limb ischemia is differentiated from those patients with an insidious onset of symptoms; these patients tend to present late and the phrase chronic limb ischemia is used to identify such a scenario. The extent of collateral flow across the site of occlusion often determines the severity of symptoms. Patients with long-standing atherosclerotic lesions often have adequate time to develop collateral channels; hence, arterial occlusion in these patients often may fall into the “chronic” category.
PATHOPHYSIOLOGY
Acute limb ischemia may occur as the result of embolization or in-situ thrombosis. Emboli originate from the heart in more than 90% of cases and normally lodge at the site of an arterial bifurcation such as the distal common femoral or popliteal arteries. The decreasing prevalence of rheumatic heart disease underlies a diminishing proportion of embolic versus thrombotic causes for acute limb ischemia. When embolization occurs, it usually does so in the setting of atrial fibrillation or acute myocardial infarction, when portions of atrial or ventricular mural thrombus detach and embolize to the arterial tree. It is often difficult to distinguish embolus from thrombosis, but embolic occlusions should be suspected in patients with the following features: (1) acute onset where the patient is often able to accurately time the moment of the event; (2) prior history of embolism; (3) known embolic source, such as cardiac arrhythmias; (4) no prior history of intermittent claudication; and (5) normal pulse and Doppler examination in the unaffected limb.
Thrombosis as an etiology for acute limb ischemia is a much more diverse category than embolization. With the increased use of peripheral arterial bypass grafts for chronic limb ischemia, and noting the finite patency rate of any bypass graft conduit, it is not surprising that acute graft occlusion is now the most frequent cause of acute lower extremity ischemia in most centers. Symptoms may be less dramatic than embolic occlusion, depending on the extent of collateral flow across the site of occlusion. In addition to the presence of collateral channels, the location of the occlusion may also play a critical role in the severity of limb ischemia. For example, occlusion of the popliteal artery results in profound limb ischemia, since it is the only artery crossing at the level of the knee. By contrast, occlusion of the anterior tibial artery is often asymptomatic because the posterior tibial and peroneal arteries can function as alternate parallel channels to supply the foot.
Irrespective of the etiology of ischemia, the end result is the build-up of toxic byproducts within the ischemic tissue bed. These toxins include the free radicals, which are oxygen-derived, chemically reactive molecules that are responsible for the injury that occurs after ischemia and reperfusion. Ischemia induces leakage of protein and fluid from the capillary bed, resulting in tissue edema. Hydrodynamic pressure in the extravascular space rises to a level that competes with venous outflow, perpetuating a vicious cycle that can eventually impede arterial inflow. At first, this process occurs at a microscopic level, but it may progress to the development of high tissue pressures at a regional level and the clinical entity known as the compartment syndrome. The development of a compartment syndrome is hastened by the abrupt reperfusion of a previously ischemic tissue bed, a phenomenon that explains the relatively frequent need for fasciotomy after lower extremity surgical revascularization for severe limb ischemia.
DIAGNOSIS
Acute limb ischemia is a clinical diagnosis. Patients complain of numbness and pain in the extremity, progressing in severe cases to motor loss and muscle rigidity. Examination reveals the absence of palpable pulses, and the location of the pulse deficit allows one to predict the site of arterial occlusion. The “5 Ps” have been used as a mnemonic to remember the presentation of a patient with acute limb ischemia—paresthesia, pain, pallor, pulselessness, and paralysis. In some cases, a sixth P is added—poikilothermia, meaning equilibration of the temperature of the limb to that of the ambient environment (coolness). The process is sometimes confused with deep venous thrombosis by an inexperienced observer. Although a deep venous thrombosis may manifest as limb ischemia when severe (phlegmasia cerulea dolens), profound lower extremity edema is uncommon in pure arterial ischemia. Occasionally, a patient with arterial ischemia and pain at rest keeps the extremity in a dependent position and edema may develop; such a scenario may be apparent if an adequate history is obtained. Pain may either be constant or elicited by passive movement of the involved extremity. History should include a description of the duration, location, intensity, and suddenness of the onset of pain and change over time. Embolic occlusions are usually quite sudden and of great intensity, such that patients often present within a few hours of onset. The past history should state whether or not the patient has a history of intermittent claudication, previous leg bypass or other vascular procedures, and history suggestive of embolic sources such as cardiac arrhythmias and aortic aneurysms. General atherosclerotic risk factors (smoking, hypertension, diabetes, hyperlipidemia, family history of cardiac or vascular events) should be recorded because these can be predictors of thrombosis.
In an effort to classify the extent of acute ischemia for standardization reporting of outcome, the Society for Vascular Surgery/International Society for Cardiovascular Surgery (SVS/ISCVS) (now SVS) ad hoc committee was established and published what has now come to be known as the Rutherford criteria, after Dr. Robert Rutherford, the lead author of the article. The following three classes were defined:
Class 1: the limb is viable and remains so even without therapeutic intervention |
Class 2: the limbs are threatened and require revascularization for salvage |
Class 3: those limbs that are irreversibly ischemic and infarction has developed such that salvage is not possible |
As examples, a patient with a palpable femoral pulse but an absent popliteal pulse is likely to have a superficial femoral artery occlusion. Absence of a femoral pulse signifies disease above the inguinal ligament, within the iliac arterial segment or the aorta itself. Patients with common femoral artery emboli maintain an easily palpable femoral pulse, sometimes even augmented with a “water-hammer” characteristic, until such time as the absence of outflow in the external iliac artery causes this vessel to thrombose and the femoral pulse to disappear. Patients with popliteal emboli, by contrast, usually have a palpable popliteal pulse but no palpable pulses below (dorsalis pedis or posterior tibial). Finally, a patient with leg ischemia secondary to a popliteal aneurysm usually demonstrates a very large and easily palpable popliteal pulse, concurrent with severe calf and foot ischemia. The popliteal pulse is maintained in these patients as a result of the events leading to occlusion—the aneurysm is associated with serial embolic events to the three crural vessels, occluding them one by one until, at the time of the last occlusion, the leg becomes ischemic. The aneurysm itself, however, remains palpable owing to the somewhat static column of blood and absent outflow.
Even the most astute clinician sometimes has difficulty in discerning his or her own digital pulse from the patient's pedal pulse. For this reason, the use of a Doppler instrument is advantageous to document flow within the smaller arteries and, most important, to provide an objective and quantitative assessment of the extent of arterial insufficiency through the calculation of a Doppler-derived ankle-brachial index (ABI). Normally, the ABI is greater than 1.0. The index is decreased to 0.40 to 0.80 in patients with claudication and to lower levels in patients with pain at rest or tissue loss. The ABI may be normal in some patients with mild arterial narrowing; treadmill exercise has been used in these cases to increase the sensitivity of the test. Patients with diabetes mellitus or renal failure may have calcific lower leg arteries, rendering them incompressible and causing a falsely elevated ABI; in these cases a toe-brachial pressure index can be measured and is more predictive of significant arterial disease.] In some centers, transcutaneous oxygen tension has also been used to assess the severity of peripheral arterial occlusion as well as to predict the most appropriate level of amputation.
Characteristic Ankle-Brachial Indices in Patients Presenting with Lower Limb Ischemia
CLINICAL CATEGORY |
ANKLE-BRACHIAL INDEX |
Normal |
>0.97 (usually 1.10) |
Claudication |
0.40-0.80 |
Rest pain |
0.20-0.40 |
Ulceration, gangrene |
0.10-0.40 |
Acute ischemia |
Usually <0.10 |
The anatomic level of the arterial stenoses can be predicted from palpation of pulses in the femoral, popliteal, and ankle regions. For example, patients with disease confined to the superficial femoral artery have a normal femoral pulse but no palpable popliteal or ankle pulses below, whereas patients with aortoiliac disease have absent femoral pulses as well. Doppler segmental pressures are also useful in defining the level of involvement; a drop in pressure of 30 mm Hg or more between two segments predicts arterial occlusion between the two levels.
Duplex ultrasound has been used in some centers to define the anatomic extent of peripheral arterial disease. Although duplex has been useful in documenting the patency of a single arterial segment such as a stented superficial femoral artery or a bypass graft, evaluation of the entire lower extremity arterial tree remains imprecise, and its adequacy as the sole diagnostic modality for planning a percutaneous or open surgical intervention remains controversial.
Contrast arteriography remains the gold standard with which all other tests must be compared. Arteriography is a semi-invasive modality, and as such its use should be confined to those patients for whom a surgical or percutaneous intervention is contemplated.
Magnetic resonance (MR) angiography is being used with greater frequency in patients with peripheral arterial disease. Using gadolinium as an MR contrast agent, the specificity and sensitivity of the test exceed that of duplex ultrasonography and approach the accuracy of standard arteriography. MR angiography has been effective in demonstrating patent tibial arteries undetected with less sensitive conventional arteriography, identifying potential target vessels for an otherwise unfeasible lower extremity reconstructive bypass procedure. Today, MR angiography is widely employed in patients with chronic renal insufficiency to limit the dye load.
Another noninvasive imaging modality, computed tomographic (CT) angiography, is gaining appeal as a means of delineating anatomy to provide a means of localizing the extent and severity of occlusive disease. With future improvements in hardware and software technology, it is likely that MR and CT angiography will effectively replace conventional diagnostic arteriography, and arterial cannulation will be reserved solely for percutaneous interventional therapies.
TREATMENT
Unlike the situation in patients with chronic limb ischemia where observation alone is a common and quite appropriate treatment option, patients presenting with acute limb ischemia often require revascularization to salvage the leg. In fact, this is why they present acutely and are often able to identify the precise time of the occlusive event, similar to the manner that a patient with a perforated peptic ulcer knows exactly when it occurred. In many cases, the paucity of preexisting collateral channels renders the limb very ischemic after thrombotic or embolic occlusion of the main arterial segment. Symptoms occur with severity and rapidity, forcing the patient to seek treatment almost immediately.
Once the diagnosis is made, adequate systemic anticoagulation is instituted. A bolus of unfractionated heparin is standard, followed by a continuous infusion to maintain the activated partial thromboplastin time (aPTT) in a therapeutic range. The goal of anticoagulation is twofold: (1) to decrease the risk of thrombus propagation and (2) in the case of presumed embolic occlusion, to prevent recurrent embolization. Occasionally, if early angiographic evaluation is feasible, heparinization can be withheld, pending the establishment of arterial access. Otherwise, a micropuncture technique (small localizing needle [21 gauge], guide wire [0.018 inch], and a 4-French sheath) is used to gain access or the anticoagulation is withheld to allow the aPTT to fall to within 1.5 times control.
The severity of the ischemic limb based on the earlier-mentioned Rutherford classification dictates the extent of diagnostic tests performed for systemic risk factor assessment. Routine blood studies and coagulation tests should be drawn before heparin is administered. Correction of underlying electrolyte imbalances and systemic anticoagulation should proceed concomitant with the other investigations. A plain chest radiograph and electrocardiogram should be obtained in every patient. In patients with suspected embolism, an echocardiogram should be obtained as soon as time allows. Despite the desire for a complete workup, the treatment of an ischemic limb must take priority over other more complex and time-consuming investigations.
Unfortunately, the threat is not only to the limb, but these patients are also at a high risk for death. Limb hypoperfusion results in systemic acid-base and electrolyte abnormalities that impair cardiopulmonary and renal function. Successful reperfusion may result in the release of highly toxic free radicals further compromising these critically ill patients. Therapeutic choices are often few, and patient expectations are not always realistic. The management of acute limb ischemia requires a thorough understanding of the anatomy of the arterial occlusion and the open surgical and percutaneous options for restoring limb perfusion.
There exist several basic therapeutic options to pursue in patients with acute limb ischemia
1. |
The first option is anticoagulation alone. If the ischemia is nonthreatening (e.g., Rutherford class 1 or 2A), such a nonaggressive course may be appropriate. Angiographic evaluation and elective revascularization may then be undertaken after the patient has been fully prepared and other co-morbidities such as concurrent coronary artery disease have been addressed. |
2. |
Patients who present with more severe ischemia (Rutherford class 2B) require some form of intervention to prevent progression to irreversible ischemia and limb loss. These patients should undergo early angiographic evaluation with adequate imaging of the affected and the unaffected extremity. Arterial access is accomplished at a site distant from the ischemic extremity using a contralateral femoral artery or brachial approach to avoid the creation of needle entry sites in an artery that might subsequently be infused with a thrombolytic agent. |
Early angiographic imaging should be undertaken in all patients, with the sole exception of those patients with common femoral emboli. These individuals can be taken directly to the operating room for embolectomy, but intraoperative completion angiography is necessary to rule out retained thromboembolic material.
Once adequate diagnostic information has been obtained from the angiogram, the clinician is in a position to make a decision on whether to pursue a percutaneous or open surgical option.
Thrombolytic therapy: Thrombolytic therapy with the plasminogen activators (urokinase, alteplase, or reteplase) has been demonstrated to lower the morbidity and mortality when compared with a traditional approach of immediate operative revascularization. These benefits appear to be especially prominent in patients with medical co-morbidities when early revascularization is necessary. The complication rate is high when such patients are taken urgently to open surgical revascularization without the ability to adequately prepare the patient for operation. |
Mechanical thrombectomy: Removal of intra-arterial thrombus with a mechanical device has gained popularity over the last several years. Some devices rely on hydrodynamic, rheolytic forces to extract the thrombus, whereas others use rotating components to fragment the clot. Mechanical thrombectomy devices can be used in conjunction with pharmacologic thrombolysis. Although the devices do result in clearing of much of the occluding thrombus, an infusion of thrombolytic agent is still necessary in many cases to remove smaller amounts of retained mural clot. |
Immediate open surgical revascularization: Early operation has been remarkably effective in restoring adequate blood flow to an ischemic extremity. The relatively simple procedure of balloon catheter thromboembolectomy, however, has fallen into disfavor for all but embolic occlusions. The underlying lesion responsible for the thrombotic event must be identified and corrected to avoid early reocclusion. For this reason, long atherosclerotic occlusions are best treated with the placement of a bypass graft. As well, patients with occlusion of a bypass graft as the cause of ischemia are best served with the placement of a new bypass graft, if at all possible.[23] |
Open Surgical Revascularization
Unfortunately, immediate open surgical interventions have been associated with an unexpectedly high risk of major morbidity and mortality. Blaisdell and associates first reported this finding, noting a 30% perioperative mortality rate in a review of more than 3000 patients in the published works from the 1960s and 1970s. Although the results have improved since the publication of Blaisdell's landmark review, mortality rates continue to remain undesirably high. This observation appears to relate to the relatively common occurrence of cardiopulmonary complications developing in these medically compromised patients, patients who are ill prepared to undergo early operative intervention. The severity of ischemia precludes adequate preoperative preparation of the patient, and complications such as perioperative myocardial infarction, cardiac arrhythmia, or pneumonia appear to underlie the unacceptable mortality rate in these patients. Additionally, wound complications and delayed healing are common in these patients. Hence, despite successful limb salvage, patient dissatisfaction is frequent.
Pharmacologic Thrombolytic Therapy
Noting the high morbidity from primary open surgical revascularization in patients suffering from true limb-threatening lower limb ischemia, three randomized, prospective clinical trials were organized to compare thrombolytic therapy and immediate open surgical revascularization.
Because the major thrombolytic trials failed to demonstrate an improved outcome for percutaneous thrombolysis compared to open surgery, clinical consensus was never achieved. Physicians continue to offer patients therapy based on their field of expertise and patient symptoms. Future advances have been redirected toward decreasing the dose and duration of thrombolytic agents to decrease the complications and mortality associated with the bleeding complications. It is hoped that by minimizing or eliminating the bleeding risks of thrombolytic therapy, this form of minimally invasive percutaneous procedure would demonstrate superior outcomes compared with open surgical revascularization. In this setting, the use of mechanical thrombectomy devices as an adjunct to pharmacologic thrombolytic therapy is gaining popularity.
Percutaneous Mechanical Thrombectomy Devices
Numerous percutaneous mechanical thrombectomy (PMT) devices are currently available in the United States for dialysis graft declotting; however, only two devices are approved for infrainguinal arterial use in the United States.
The devices may be classified into “aspiration” or “microfragmentation-only” devices. The latter embolize the microfragments that are created by the mechanical component of the device. Many of these devices were designed primarily for dialysis graft declotting, where embolization is not seen as a device limitation. However, when used for peripheral arterial occlusion, the risk of downstream embolization is clinically significant. A few of the PMT devices also function as “wall-contact” types.
The potential benefits of these devices include the minimally invasive nature of the procedure, rapid blood flow restoration, and a decrease in the dose and duration of adjunctive pharmacologic thrombolytic agents. The two devices approved for peripheral vascular application are described in the following sections.
Chapter 67 - Arterial Thromboembolism
SCOTT R. FECTEAU, MD R. CLEMENT DARLING III, MD SEAN P. RODDY, MD
HISTORICAL BACKGROUND
In 1854, Virchow was the first to use the term embolus in the description of sudden obstruction of an artery by material that originated from a distal site. The term is derived from “embolos,” a Greek term meaning plug. The occlusive material may consist of platelet-fibrin thrombus, cholesterol debris, laminated aneurysmal thrombus, or a foreign body that has gained access to the vascular system.
Originally, the treatment of an arterial embolus was solely observational, which eventually terminated in limb loss or death. In the early 1900s, the initial successful reports of surgical removal of embolic material were described and operative management slowly gained acceptance. These early manuscripts documented the necessity for early intervention to avoid irreversible intimal damage and secondary thrombosis of vessels distal to the point of embolic occlusion. One of the great advances in treatment of patients with thromboembolism was the introduction of heparin for use before, during, and after surgical intervention. Intravenous heparin infusions decreased the propagation of thrombus, stabilized the clot, and recruited collateral vessels.
Early in its evolution, the complete removal of thromboembolic material, especially when associated with large amounts of propagated thrombus, remained problematic. A variety of methods, including suction catheters, vigorous arterial flushing, and external compression on the limbs, were used with moderate success. In 1963, Fogarty and associates proposed the use of a balloon catheter that offered a significant advance for the retrieval of thrombus, distal and proximal to the embolic site. For the first time, intravascular thromboembolic material could be removed from a single, strategically placed arteriotomy, with relatively little trauma to the vessels.
The mortality associated with acute peripheral arterial occlusion remains high, averaging 10% to 25%. Advanced age, severity of associated medical problems, and presence of coexisting chronic arterial occlusive disease have offset improvements in the management of atherosclerotic heart disease despite technical advances in performing thromboembolectomy. In the past, patients presenting with acute peripheral arterial occlusion were most often in the 5th decade of life. This represents an era when rheumatic heart disease, associated mitral valvular deformity, and resultant peripheral embolization were the most common causes of ischemia. More recent data demonstrate that the mean age of patients with acute peripheral arterial occlusion is 70 years, reflecting a shift in etiology from rheumatic to atherosclerotic heart disease and the increased frequency of peripheral atherosclerosis as an inciting cause for occlusion.
CLASSIFICATION OF PERIPHERAL ARTERIAL EMBOLI
Arterial emboli can be classified on the basis of size, content, and site of origin. Although somewhat arbitrary, an understanding of this classification is important because clinical presentation, natural history, and management can vary based on the type of embolus.
Macroemboli
Cardiac Emboli
Macroemboli arise from the dislodgement of a large plaque or mural thrombus and result in large single-vessel occlusions. The heart is by far the predominant source of spontaneous arterial macroemboli, cited in 80% to 90% of cases. Although this statistic has remained constant over the last half-century, there has been a shift in the underlying heart disease from rheumatic valvular disease to atherosclerotic coronary vascular disease. Presently, atherosclerotic heart disease has been implicated as a causative factor in 60% to 70% of all cases of embolus, with rheumatic mitral valve disease and associated atrial fibrillation in the remaining 30% to 40%.
The close association of atrial fibrillation with modern-day heart disease may explain the rather constant appearance of arterial emboli despite the markedly diminished incidence of rheumatic disease.[45] Regardless of the cause for atrial fibrillation, this dysrhythmia is currently associated with two thirds to three fourths of peripheral emboli. As a result of stasis, clot formation is particularly common in the left atrial appendage. In this location, transthoracic echocardiographic techniques have had only intermediate success in thrombus detection.] Although transesophageal echocardiography offers a more thorough and accurate evaluation of the heart, the sensitivity of this modality has also been disappointing. Consequently, the absence of detected thrombus does not rule out the heart as a potential source. Next to atrial fibrillation, myocardial infarction is the second most frequent entity associated with peripheral arterial embolization. In a series of 400 patients with peripheral emboli, Panetta and coworkers determined that myocardial infarction was the causative factor in 20%. Thrombus within the left ventricle most frequently follows an anterior transmural myocardial infarction. Despite the frequent presence of left ventricular thrombus, the incidence of embolization is less than 5% in this patient population. Darling and associates reported on the timing of embolic complications in relation to the initial cardiac insult. They noted a lag in the development of symptoms, ranging from 3 to 28 days, with a mean of 14 days. Electrocardiographic changes were noted in 64% of all patients presenting with acute extremity ischemia requiring surgical intervention. The presence of electrocardiographic changes predicted a higher morbidity and mortality.
Occasionally, embolic symptoms may be the first clinical manifestation of a “silent myocardial infarct.” This adds to the importance of careful evaluation of the electrocardiogram and serum cardiac enzymes of patients presenting with acute ischemic syndromes. Delayed presentation of emboli originating from the heart as a result of myocardial infarction is frequently associated with the formation of a left ventricular aneurysm. Thrombus has been identified in 50% of cases, with 5% experiencing peripheral embolization. Coincidentally, it is the sheer magnitude of the prevalence of coronary artery disease that makes this a common cause of arterial emboli.
Cardiac valvular prostheses are another common source of emboli. Thrombus formation may occur around the sewing ring in a caged-ball or caged-disc valve. Tilting-disc valves predispose to thrombus formation at the hinge points, which correspond to sites of low-velocity blood flow. Permanent anticoagulation therapy is required in patients with prosthetic mechanical valves, and embolic complications are particularly common when postimplantation anticoagulation is inadequate or discontinued. Biosynthetic valves, such as the porcine xenograft, are not as thrombogenic as prosthetic valves, and anticoagulation may not be required.
Intracardiac tumors, such as atrial myxomas, are a rare source of peripheral arterial emboli. Similarly, vegetations from mitral or aortic leaflets in patients with bacterial or fungal endocarditis can also be a cause. Despite the improved spectrum of antibiotic regimens, the incidence of endocarditis has increased largely as a result of intravenous drug abuse. This etiologic factor should be suspected in younger patients and in those without a history of atherosclerotic or rheumatic heart disease. Histologic examination of the surgical embolic specimen may provide a clue as to the etiology of the insult, especially if leukocytes or bacteria are visualized in the material.
Noncardiac Emboli
Spontaneous emboli originating from noncardiac sources are noted in 5% to 10% of patients. Noncardiac emboli often originate from atherosclerotic disease of more proximal vessels. Thrombi arising from mural erosions can be large and produce a clinical picture indistinguishable from emboli of a cardiac origin. Downstream embolization of mural thrombus associated with aortoiliac, femoral, or popliteal aneurysms has been reported. Proximal aneurysms in the upper extremity as a result of thoracic outlet syndrome may also contribute to the incidence of this phenomenon.
Noncardiac tumors and other foreign bodies may gain access to the arterial circulation and form arterial emboli. This event is more commonly noted in tumors that tend to invade the pulmonary vasculature or heart, such as primary or metastatic lung carcinoma. Bullet emboli have also been reported.
“Paradoxical embolization” occurs when a thrombus arising within the venous circulation passes from the right side of the heart to the left side through an intracardiac communication, most often a patent foramen ovale, to become an arterial embolus. This scenario most commonly occurs after the occurrence of a pulmonary embolism, in which acute pulmonary hypertension is associated with the development of a right-to-left shunt.
In addition to venous-derived thrombus, tumor and foreign body paradoxical emboli have been reported. Mixed symptoms of arterial and venous obstruction, and a history of deep venous thrombosis or pulmonary embolism in a patient presenting with acute arterial occlusion should prompt consideration of this entity. Echocardiography and cardiac catheterization are helpful to identify the right-to-left shunt and to accurately define its location.
SITES OF EMBOLISM
Approximately 20% of emboli eventually affect cerebrovascular circulation, and 10% involve the visceral vessels. It is likely, however, that embolization to these sites is markedly underdiagnosed. Acute strokes secondary to cerebrovascular emboli may be attributed to other pathologic causes. Similarly, large visceral emboli can be rapidly fatal and may frequently be confused with other causes of sudden intra-abdominal catastrophies.
The axial limb vasculature is involved in 70% to 80% of all embolic disease. Emboli lodge within the lower extremities five times as often as in the upper extremities. The abrupt change of vessel diameter at branching sites makes these areas the most common locations of embolic occlusions. The increasing incidence of occlusive disease in our aging population produces multiple areas of stenosis unrelated to a bifurcation that can also serve as anchoring sites for emboli. The presence of preexisting collateral vessels may provide enough distal circulation to prevent severe ischemic symptoms, adding to the confusion in discriminating between embolization and thrombosis overlying an atherosclerotic stenosis.
Overall, the femoral bifurcation is the most frequent site of embolic occlusion, noted in 35% to 50% of cases. The popliteal artery is the second most frequent site and, taken together, the femoral and popliteal arteries are involved more than twice as often as the aorta and iliac vessels. This reflects the simple mechanical fact that only a thrombus of considerable size can lodge at the aortic or iliac bifurcation unless it occurs in the setting of significant aortoiliac occlusive disease.
PATHOPHYSIOLOGY
The clinical outcome of an embolic event depends mainly on the size of the vessel involved, the degree of obstruction, and, most important, the amount of collateral blood flow. If an acute embolus obstructs a previously normal artery, severe distal ischemia may result owing to the paucity of collateral pathways. In contrast, sudden occlusion from an embolus imposed on a severely stenotic vessel may produce only mild clinical symptoms owing to previously well-established collateral vessels. The latter is also characteristic of acute arterial thrombosis in the setting of advanced atherosclerosis and can confuse the differential diagnosis. Historically, a great deal of emphasis has been placed on intervention within the 4 to 6 hours following onset of symptoms, because this was thought to represent the maximal length of tolerable ischemia. It is now well recognized that no arbitrary time limit can be imposed on the timing of interventions. The physiologic state of the limb, determined mainly by a balance between metabolic supply and demand, rather than the elapsed time from the onset of occlusion is the best predictor of limb salvage. Again, supply to the affected tissues is determined largely by preexisting collateral vessels.
Following arterial obstruction by an embolus, three possible events may occur to aggravate ischemia. Of primary importance is propagation of thrombus. Linton described proximal and distal thrombus propagation in 1941. The extension of thrombus markedly impairs the collateral circulation and thus represents a major secondary factor worsening ischemia. Effective surgical therapy depends on complete removal of all propagated thrombus. Clot can form in a discontinuous fashion, which makes cannulation of the distal vasculature necessary at the time of embolectomy. The prevention of the thrombus propagation and the protection of the collateral circulation are the primary reasons for early and aggressive anticoagulation. Also, the presence of backbleeding at the time of embolectomy is an unreliable guide to the patency of distal circulation because it may occur from intervening arterial branches proximal to distal clot.
A second event that may aggravate distal ischemia is fragmentation of an embolus resulting in migration of debris into the distal circulation. Occasionally, however, partial clot lysis and fragmentation may be the mechanism for the spontaneous clinical resolution of an embolic event.
Additionally, associated venous thrombosis may occur in the setting of prolonged arterial ischemia. This is presumably due to a combination of sluggish flow and ischemic injury to the intima of the involved veins. Development of venous thrombosis may further reduce arterial blood flow and worsen edema following revascularization. In fact, pulmonary embolism has been historically cited as a significant cause of mortality in patients initially suffering from arterial thromboembolism.[20][81]
Patients with severe ischemia resulting from embolic occlusions are susceptible to several systemic and metabolic complications. Haimovici estimated that one third of the deaths from peripheral arterial thromboembolism occur as the result of metabolic complications following revascularization.[82] High concentrations of potassium, lactic acid, myoglobin, and cellular enzymes, such as serum glutamic oxaloacetic transaminase, are found in the venous blood of a severely ischemic limb and result largely from rhabdomyolysis. In a series of patients with acute limb ischemia, the mean venous effluent pH was 7.07, whereas the serum potassium level was elevated to 5.77 mEq/L 5 minutes after surgical embolectomy.[83] After revascularization, the sudden release of these accumulated products into the systemic venous circulation has profound consequences. The triad of peripheral muscle infarction, myoglobinemia, and myoglobinuric renal failure characterizes the reperfusion syndrome. Hyperkalemia, metabolic acidosis, and myoglobinuria are the key features of the syndrome. Renal tubular necrosis may occur when myoglobin is precipitated in the renal tubules under acidotic conditions. Although volume repletion, free radical scavengers, and urinary alkalinization have been the recommended treatments, it now appears that once appropriate volume expansion has been achieved, the addition of free radical scavengers and bicarbonate may be unnecessary.
Significant local effects of ischemia reperfusion can contribute to morbidity and limb loss despite successful extraction of thrombus. Edema often follows revascularization owing to compromised integrity of the capillary wall occurring to a degree proportional to the duration and severity of ischemia. Capillary disintegrity results from both the ischemic insult itself and the effects of reperfusion. Large quantities of oxygen free radicals are released and tend to overwhelm the intracellular scavenger systems, causing damage to the phospholipid cell membrane and other intracellular organelles. Cell membrane damage results in the transudation of fluid into the interstitial space, producing edema. Substantial edema can further reduce local perfusion and exacerbate tissue injury. The no-reflow phenomenon occurs as a result of massive edema into a fixed space (the compartment syndrome) and capillary endothelial cellular edema with consequent vascular obstruction. Under these conditions, peripheral tissue hypoperfusion persists despite adequate large-vessel revascularization, and large-vessel reocclusion can occur rapidly. Although fasciotomy may correct the compartment syndrome, small-vessel obstruction is more difficult to ameliorate.
CLINICAL PRESENTATION
The sudden onset of arterial ischemia is often manifested by some or all of the five cardinal signs denoted by the “five Ps”: pulselessness, pain, pallor, paresthesia, and paralysis. Temperature changes are often described as poikilothermic, thus adding a sixth P to the mnemonic. Although the five Ps may be a useful axiom for instruction of house staff, these characteristics represent the nonspecific results of acute arterial occlusion. Considerable diagnostic acumen is required to gauge the severity of ischemia.
The sudden onset of pain associated with loss of a previously palpable pulse is the hallmark of arterial embolism. In the absence of significant preexistent atherosclerosis, the site of occlusion can be accurately determined from a careful physical examination of the extremity. Here, common femoral emboli are associated with a palpable femoral pulse but absence of the popliteal pulse and commonly with a normal pulse examination on the contralateral limb. By contrast, a popliteal embolus is associated with a palpable popliteal pulse, absent pedal pulses, and coolness beginning at the level of the lower leg. Practically, however, the prior pulse status of the limb is often poorly documented or may be abnormal at baseline because of preexisting atherosclerosis. Additionally, a normal or even hyperdynamic pulse may be felt at the actual site of embolic occlusion, representing the transmitted pulse waves through fresh thrombus.
Pain is characteristically severe and steady. Typically, the major muscle groups below the level of obstruction become symptomatic and progressively worsen at locations increasingly distal to the point of occlusion. For instance, symptoms from a common femoral embolus begin with pain and numbness in the toes, rapidly progressing to involve the tissues of the calf and thigh. Focal tenderness over a muscle group can be an ominous sign, signifying advances in muscle ischemia. Occasionally, however, sensory disturbances secondary to ischemic neuropathy predominate and may mask primary complaints of pain.
The skin distal to the occlusion initially takes on a pale or waxy appearance. With time, pallor progresses to blotchy mottled areas of cyanosis. If left untreated, the skin changes proceed to necrosis and desquamation.
As mentioned previously, sensory disturbances can predominate and may mask the primary complaints of pain. In these situations, the patient may complain of numbness or paresthesias, without a prominent component of pain. The sensory changes occur as a result of ischemia of nerve tissue, which is particularly sensitive to ischemic insult.
Paralysis is, at first, the result of motor nerve ischemia, but subsequent muscle ischemia compounds the problem. The extent of the motor deficit is a good index of the degree of tissue anoxia and correlates well with ultimate prognosis. Complete motor paralysis is a late symptom signaling impending gangrene, representing a combination of both end-stage muscle and neural ischemia. When paralysis proceeds to rigor and the initial “doughy” consistency of the muscle progresses to “woody” hardness and involuntary muscle contracture (rigor), irreversible ischemia has developed. Although the limb may be salvaged, ultimate function is severely compromised and the systemic metabolic consequences of revascularization may be lethal.
A point of temperature demarcation can usually be noted approximately one joint distal to the point of occlusion. For example, temperature change just above the ankle often denotes occlusion at the popliteal bifurcation, whereas such a finding at or just above the knee suggests blockage at the femoral bifurcation. Changes in the upper thigh on one side suggest an iliac occlusion, and involvement of both thighs, lower abdomen, or buttocks suggests an aortic bifurcation saddle embolus.
Careful history and physical examination can provide useful data for stratifying acutely ischemic limbs for therapeutic purposes. Clinical findings and assessment of distal arterial and venous Doppler signals allow limbs to be categorized into the following clinically relevant groups: (1) viable, (2) threatened, and (3) irreversibly ischemic. These categories were formulated and revised by the Society for Vascular Surgery/International Society for Cardiovascular Surgery (SVS/ISCVS) committee on reporting standards.[89]
1. |
Viable: not immediately threatened. There is no ischemic pain, no neurologic deficit, adequate skin capillary circulation, and clearly audible Doppler pulsatile flow signal in pedal arteries (ankle pressure > 30 mm Hg). |
2. |
Threatened viability: indicates a state of reversible ischemia provided arterial obstruction is promptly relieved. Ischemic pain or mild and incomplete neurologic deficit is present. Pulsatile flow in pedal arteries is not audible with Doppler, but venous signals are demonstrable. |
3. |
Irreversible ischemic change: profound sensory loss and muscle paralysis, absent capillary skin flow, muscle rigor, and skin marbling are characteristic. Neither arterial nor venous flow is audible; major amputation is required, regardless of therapy. |
THERAPY
Optimal therapy in most cases of arterial embolism is prompt surgical removal by embolectomy. However, knowledge of available surgical options, pharmacologic (primarily thrombolytic) therapies, and mechanical thrombectomy devices can allow one to delineate the most appropriate treatment path for individual patients. No large prospective, randomized trials have compared the various therapeutic options in the treatment of embolic lower extremity ischemia, and each has advantages and disadvantages. Ultimately, the therapeutic modality chosen should be based on (1) the clinical status of the leg, (2) the degree of thrombus propagation, and (3) the medical condition of the patient.
Surgical Modalities
Ideal treatment of an arterial embolus consists of expeditious diagnosis of acute arterial ischemia, recognition of the embolic source, rapid systemic anticoagulation, and surgical embolectomy. Embolectomy was popularized with the advent of the Fogarty embolectomy catheters in 1963 prior to which only 23% of arterial emboli were treated with an embolectomy technique. In contrast, 88% of emboli were treated with surgical embolectomy between 1964 and 1980.
Timely operative intervention is the goal, and preoperative preparation should be minimal once the diagnosis of embolus is made. Baseline laboratory studies should include complete blood count, serum electrolytes, blood urea nitrogen and creatinine, baseline cardiac enzymes, coagulation parameters, and blood typing with cross-matching. The use of local anesthesia and limited incisions is helpful in decreasing the operative risk in critically ill patients. Adequate communication between the anesthesiologist and surgeon should eliminate unexpected changes in the hemodynamic state. Additionally, prolonged procedural times are likely detrimental to outcome.
Intraoperative Thrombolytic Therapy
An alternative method for dealing with retained distal tibial and small-vessel thromboembolic material that is not amenable to conventional catheter techniques is the intraoperative use of fibrinolytic agents. Recent surgical procedures are traditionally viewed as a strong contraindication to thrombolytic therapy because of a high incidence of bleeding complications. In separate studies, however, Comerota and Quiсones-Baldrich have shown that infusion of thrombolytic agents during operative procedures is safe and often beneficial. Experimental work has demonstrated that blood flow is improved and salvage of ischemic muscle is accomplished with less reperfusion edema and cellular injury when lytic agents are infused. This result, which is presumably due to restoration of perfusion in the small arteriolar branches of larger axial vessels, is not possible with mechanical catheter thromboembolectomy.
The specific agents used, the dosages infused, and the method of infusion vary considerably. Urokinase was the thrombolytic agent used most frequently and appeared to be faster and safer than streptokinase. Recombinant tissue plasminogen activator and reteplase have also been administered with success. Urokinase (250,000 to 500,000 IU) is infused into the distal vasculature, either as a bolus or as an infusion over approximately 30 minutes. Arteriography is then repeated to assess the results. Gonzalez-Fajardo and associates prospectively evaluated 66 patients undergoing balloon embolectomy, 31 of whom received 250,000 units of urokinase intraoperatively.[109] They noted a statistically significant improvement in the ankle-brachial index in these patients, but this hemodynamic improvement did not translate into a reduction in the rate of amputation. Despite these findings, others have noted clinical improvement after regional infusion of thrombolytic agents for acute limb ischemia, and the technique remains promising.[103][110] Comerota and White[111] reported on 53 patients with persistent ischemia due to extensive distal thrombosis despite maximal efforts with catheter thrombectomy. Use of adjunctive regional intraoperative lytic therapy resulted in limb salvage in 70% of patients. In this series, only 1 patient (2%) had a major bleeding complication.
Endovascular Modalities
Thrombolytic Therapy
Catheter-directed thrombolytic treatment strategies were popularized in the 1970s by Dotter. Thrombolysis offers several potential advantages over surgical therapy, including its ability to dissolve platelet-fibrin aggregates in the microcirculation and collateral vessels, which are beyond the reach of catheters. Furthermore, more gradual reperfusion may help avoid the sudden reperfusion syndrome associated with sudden release of arterial obstruction. Finally, thrombolysis has the added advantage of revealing underlying arterial stenosis, which is potentially manageable via endovascular means.
Unfortunately, thrombolysis exposes the patient to the risk of potential hemorrhage, stroke, renal dysfunction, and delayed reperfusion injury leading to irreversible ischemia.
Although thrombolytic therapy can be used successfully in patients with embolic arterial occlusion, just as it can in patients with in-situ thrombosis, the indications for lytic therapy remain vague and the risks substantial.
Percutaneous Mechanical Thrombectomy
Percutaneous thrombectomy has the potential to offer the advantage of a less invasive means of accomplishing thrombectomy while avoiding the delayed reperfusion and risk of bleeding associated with lytic therapy. A variety of percutaneous thrombectomy devices have been evaluated both in vitro and clinically.
Ultrasound-Accelerated Thrombolysis
Ultrasound energy can be used to ablate thrombus by an effect described as acoustic cavitation or to improve the delivery and efficacy of a thrombolytic agent.[140][141] This has been shown in-vitro with both intravascular (catheter-based) and extravascular (transdermal) devices.[142][143] The effects of ultrasound are dependent on the frequency employed. Low-frequency transducers are associated with a great range of tissue penetration and are suitable for transdermal applications; high-frequency devices are used with intravascular devices in catheter-based systems. Although ultrasound improves the rate of thrombolysis, tissue heating is a major concern. Clinical applicability awaits a demonstration of safety and efficacy in early feasibility trials presently being organized.
Compartment Syndrome
Following revascularization, significant limb swelling may occur. This situation has the potential to result in a compartment syndrome, most frequently in the anterior compartment. Edema within closed fascial compartments can lead to neurologic compromise or impairment of distal blood flow. If prolonged severe ischemia has existed prior to embolectomy, the surgeon may elect to perform a fasciotomy empirically in conjunction with the embolectomy. Alternatively, because a fasciotomy can be easily performed subsequent to the embolectomy, some surgeons prefer a course of careful observation. Although the diagnosis of compartment syndrome is largely based on clinical assessment, the use of compartment pressures may provide some insight into the relative risks of observation versus immediate fasciotomy.
Four-compartment fasciotomy is best performed with a two-incision technique. The anterior and lateral compartments are opened through a lateral incision, and the posterior compartments are decompressed through a medial incision. These incisions are left open for delayed primary closure or skin grafting when edema resolves. The major risks associated with fasciotomies include both infection and bleeding.
SUMMARY
Despite treatment advances, acute peripheral arterial thromboembolism is still associated with substantial morbidity and mortality. Most of these patients are older, have significant co-morbidities, and have an underlying cause for the process. Emboli most commonly originate from the heart or as a result of an intra-arterial manipulation. Thrombosis in situ may develop in the setting of an underlying atherosclerotic stenosis or as a result of a hypercoagulable state. Recently, thrombosis of a bypass graft has become a more common cause of acute ischemia of the extremity.
Arterial embolization must be distinguished from acute arterial thrombosis that is due to preexisting occlusive disease. Preoperative arteriography is helpful in all but the most straightforward cases, provided ischemia is not unduly prolonged. Prompt treatment is the rule; delays in therapy unquestionably result in less favorable results. Long-term anticoagulation is mandatory in patients with embolic disease and in many cases of thrombotic occlusions of bypass grafts and native arteries.
Despite technologic advances, the morbidity and mortality rates of acute peripheral artery thromboembolism are likely to remain significant owing to an increase in the age and fragility of the population experiencing these events. Appreciable improvements in clinical outcome will be realized only through rapid diagnosis of peripheral thromboembolism, the use of appropriate surgical or endovascular interventions to restore arterial perfusion, and efficient perioperative care to address the myriad of metabolic problems encountered in this group of patients.
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