| Marc E Mitchell, MD Emile R Mohler III, MD Jeffrey P Carpenter, MD |
Dec 15, 1998 |
The management of acute arterial occlusion remains a challenge for vascular surgeons. Surgical thromboembolectomy and bypass grafting have been the mainstays of therapy for many years [1]. Recently, thrombolytic therapy and percutaneous transluminal angioplasty (PTA) have become treatment options for selected patients. Despite these advances, however, the morbidity, mortality, and limb loss rates from acute lower extremity ischemia remain high. Thus, regardless of the treatment modality used, early diagnosis and rapid initiation of therapy are essential in order to salvage the ischemic extremity.
This card will review the major causes and management approaches to acute arterial occlusion of the extremities. Acute occlusion involving the viscera is discussed separately. (See "Diagnosis and treatment of thromboembolic renal infarction").
ETIOLOGY OF ACUTE ARTERIAL OCCLUSION ！ Acute arterial occlusion can be the result of emboli from a distant source, acute thrombosis of a previously patent artery, or direct trauma to an artery (show table 1).
Arterial emboli ！ Eighty percent of arterial emboli originate in the heart and travel to the extremities; the lower extremities are affected much more frequently than the upper extremities [2]. The majority of these emboli occur in patients with significant underlying cardiac disease; the severity of the patient's underlying cardiac condition may increase the risk of surgery, and limit the options available for restoring blood flow to the ischemic extremity.
Potential sources of emboli from the heart include ventricular thrombus formation following myocardial infarction, and atrial thrombus in patients with atrial fibrillation. Up to 75 percent of patients with emboli to the lower extremities have a history of recent myocardial infarction or atrial fibrillation. (See "Echocardiography in detection of intracardiac sources of embolism").
Arterial to arterial embolization of thrombus or plaque originating from aneurysms or atherosclerotic lesions is another well described occurrence and accounts for 20 percent of peripheral emboli. Emboli typically lodge where there is an acute narrowing of the artery, such as an atherosclerotic plaque or a point where the vessel branches; the common femoral, common iliac, and popliteal artery bifurcations are the most frequent locations. In a large series of arterial embolism, for example, the following frequencies were noted [3]:
• Femoral ！ 28 percent
• Arm ！ 20 percent
• Aortoiliac ！ 18 percent
• Popliteal ！ 17 percent
• Visceral and other ！ 9 percent each
In comparison to clot emboli, atheroemboli are less likely to produce symptoms of acute arterial occlusion. Atheroemboli are typically nondistensible and irregularly shaped; as a result, they tend to produce incomplete occlusion with secondary ischemic atrophy. (See "Clinical characteristics of renal atheroemboli").
Arterial thrombosis ！ Thrombosis of a previously patent but stenotic artery is a well known complication of atherosclerosis. Occlusion of atherosclerotic vessels may occur by two mechanisms:
• Progressive atherosclerotic narrowing of the artery, with resultant low flow, stasis, and eventual thrombosis
• Intraplaque hemorrhage and local hypercoagulability (see "The role of plaque rupture in acute coronary syndromes")
The ischemia resulting from arterial thrombosis in the face of underlying atherosclerosis is usually less severe than that following an acute embolus. This difference is primarily due to the collateral circulation that develops over time in patients with atherosclerosis and chronically narrowed vessels. Collaterals are frequently so extensive that patients notice no change or only a mild increase in their symptoms of chronic ischemia when a major atherosclerotic vessel becomes occluded.
Arteritides, ergotism, and hypercoagulable states can also result in arterial thrombosis, occlusion, and acute extremity ischemia. While these conditions most frequently affect the venous circulation, certain hypercoagulable states favor arterial thrombosis (eg, antiphospholipid antibodies and hyperhomocysteinemia). (See "Clinical manifestations and diagnosis of the antiphospholipid antibody syndrome").
Arterial trauma ！ Acute arterial occlusion complicating vascular or cardiac diagnostic and interventional procedures has become a more frequent cause of acute extremity ischemia. (See "Complications of diagnostic cardiac catheterization"). The incidence of arterial complications following interventional cardiac catheterization (including hematomas, arteriovenous fistulae, pseudoaneurysms, arterial occlusion, and cholesterol emboli) has been reported to range from 1.5 to 9 percent [4]. Although acute arterial occlusion occurs in less than one percent of interventional catheterization procedures, this complication demands immediate surgical consultation [5]. Intimal flaps and dissections are frequently the cause of the occlusion, and operative repair of the vessel is required. Thromboemboli can also develop at the sheath site or catheter tip, with embolization occurring during sheath removal.
CLINICAL EVALUATION ！ A thorough history and physical examination is the first step in the evaluation of the patient with acute extremity ischemia [6]. The five "P's" of acute ischemia are:
• Pain
• Pulselessness
• Pallor
• Paresthesias
• Paralysis
Pain ！ Pain associated with acute ischemia is usually located distally in the extremity, gradually increases in severity, and progresses proximally as the length of ischemia increases. Later, the pain may decrease in severity due to progressive ischemic sensory loss.
It is essential to determine if the patient had symptoms of chronic ischemia before the acute event occurred. Patients with an embolus usually have no preexisting ischemic symptoms, and can frequently pinpoint the exact time that symptoms began. Thus, the sudden and dramatic development of ischemic symptoms in a previously asymptomatic patient is most consistent with an embolus, while gradually increasing symptoms in a patient with chronic ischemia is indicative of thrombosis.
Pulse ！ The quality and character of the peripheral pulses must be evaluated. If pulses are not palpable, a hand held Doppler should be used. It is rare to have limb threatening ischemia without a major pulse deficit.
The status of the pulses in the contralateral extremity is also important. The presence of a pulse deficit in an asymptomatic contralateral extremity is an indication of underlying chronic arterial occlusive disease and suggests that acute thrombosis of an already diseased vessel is the most likely cause of the acute occlusion. By contrast, the presence of normal pulses in the contralateral extremity suggests the absence of chronic occlusive disease, and increases the likelihood that an embolus is the etiology of acute occlusion.
Skin ！ 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 and pale with delayed capillary filling. The level of arterial obstruction is usually one joint above the line of demarcation between the normal and ischemic tissue. Both extremities should also be examined for signs of chronic ischemia such as atrophy of the skin, hair loss, and thickened nails.
Neurologic examination ！ A careful neurologic examination must be performed. Subjective sensory deficits such as numbness or paresthesias are signs of early nerve dysfunction secondary to ischemia. Major loss of sensory or motor function is indicative of advanced ischemia. The anterior compartment of the lower leg is most sensitive to ischemia, and sensory deficits over the dorsum of the foot are often the earliest neurologic sign of vascular insufficiency.
CLASSIFICATION OF ACUTE EXTREMITY ISCHEMIA ！ The Society of Vascular Surgeons (SVS) and International Society of Cardiovascular Surgeon (ISCVS) have developed a standardized method for categorizing and reporting acute limb ischemia based upon clinical examination [6,7]. Extremities are placed in one of three categories based upon these clinical findings to help judge the severity of ischemia (show table 2):
• Viable limbs are under no immediate threat of tissue loss.
• Threatened limbs have reversible ischemia, but immediate relief of the arterial occlusion is required if the extremity is to be salvaged and major amputation avoided.
• Nonviable extremities have irreversible ischemia and will require major amputation regardless of the therapy that is instituted. Revascularization of the nonviable extremity may be required to allow healing of the amputation or to permit amputation at a lower level.
DIAGNOSTIC TESTS ！ Arteriography is the diagnostic procedure that provides the most useful information in the setting of acute arterial occlusion. In addition to demonstrating detailed 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 which 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 visualized as a sharp or tapered, but not rounded, cutoff on arteriography. Diffuse atherosclerosis with well developed collateral circulation is generally present.
Although all patients with acute extremity ischemia would benefit from the information obtained from arteriography, it is not possible to perform this test in every case. Patients with a threatened extremity, for example, cannot tolerate the several hour delay in revascularization while arteriography is being performed. Thus, patients with a viable extremity should generally undergo diagnostic arteriography, while those with a threatened extremity should have immediate surgical revascularization with intraoperative arteriography as necessary.
TREATMENT ！ It is difficult to compare published results of the treatment of acute extremity ischemia because of different methods used to describe the severity of ischemia and differences in the duration of ischemia. However, it is clear that acute extremity ischemia is associated with a high hospital morbidity and mortality and high rates of limb loss. Limb loss rates as high as 30 percent and hospital mortality as high as 20 percent have been quoted in surgical series [1]. Cardiopulmonary complications account for the majority of the deaths, underscoring the severity of the baseline medical condition of these patients.
The best defense against limb loss is prompt initiation of therapy. Thus, once the diagnosis of acute arterial occlusion has been made by history and physical examination, the Fifth ACCP Consensus Conference on Antithrombotic Therapy recommends that the patient should immediately receive 10,000 units of intravenous heparin followed by a continuous heparin infusion [8]. Anticoagulation will prevent further propagation of thrombus, and inhibit thrombosis distally in the arterial and venous systems due to low flow and stasis. Time is crucial; the decision to administer heparin is based upon the clinical evaluation and should not be delayed while waiting for diagnostic procedures to be performed.
Following the initiation of heparin, treatment then varies depending upon the viability of the limb. Options include surgery and thrombolytic therapy.
Patients with threatened extremities ！ Patients with a threatened extremity should undergo emergent surgical revascularization. The majority of these patients have had an embolic event, and irreversible changes can occur within as little as four to six hours of profound ischemia. While pharmacologic thrombolysis may successfully dissolve the embolus (see below), the time required is usually too long to allow this to be an acceptable alternative to surgery.
At surgery, an embolus will be found in the majority of patients. Embolectomy is usually all that is required to relieve the occlusion and provide adequate blood flow to the extremity. Most surgeons perform an intraoperative completion arteriogram after the embolectomy to evaluate the adequacy of distal blood flow. Intraoperative thrombolytic therapy may also be used if there are small emboli in the distal runoff vessels. Depending upon the length and severity of the ischemia, a fasciotomy may be required to prevent the development of a compartment syndrome.
Patients with viable extremities ！ Intraarterial thrombolysis has recently become an alternative to surgical therapy in patients with ischemic but viable extremities [9,10]. Technical success rates in achieving thrombus dissolution approach 70 percent with this technique, and limb salvage rates similar to those of surgical series have been reported [10,11,12]. However, the usefulness of thrombolytic therapy is limited by the severity of the ischemia, and the length of time required to achieve dissolution of the thrombus.
Recently, several randomized, prospective clinical trials have been published comparing surgical revascularization to thrombolytic therapy in the treatment of acute ischemic but viable lower extremities [12,13,14,15].
• A randomized, prospective, double blind study of thrombolysis or peripheral arterial surgery (TOPAS) was performed in 544 patients who had acute lower extremity ischemia for 14 days or less [13,16]. Phase 1 of this trial compared three different doses of catheter directed recombinant urokinase (rUK) and found that a dose of 4000 IU/min for four hours, followed by 2000 IU/min for a maximum of 48 hours provided the maximum lytic efficacy at a minimal bleeding risk [13]; recanalization was achieved in 79.7 percent and in 67.9 percent there was complete lysis of thrombus [16].
When comparing the patients receiving this dose of rUK with those having surgery, the one year mortality rate amputation-free survival rates did not differ significantly [16]. Thrombolysis and surgery were of similar benefit for treating occlusion of native arteries or bypass grafts. Major (including intracranial) hemorrhages were more common with rUK (12.5 versus 5.5 percent, respectively). Among the patients who received rUK, 40 percent required subsequent surgery at 6 months; however, there was a reduced requirement for complex surgery after thrombolytic therapy.
• The STILE trial consisted of 393 patients with nonembolic arterial and graft occlusion who were randomized treatment to surgery or intraarterial catheter directed thrombolysis with recombinant tissue plasminogen activator or urokinase [14]. Failure of catheter placement occurred in 28 percent of patients randomized to thrombolytic therapy. Patients with ischemia of 14 days or less who were treated with thrombolysis had improved amputation-free survival and shorter hospital stays compared to the surgical group. By contrast, surgical revascularization was more effective and safer in patients with ischemia for longer than 14 days. For the patients receiving thrombolysis who subsequently required surgery, the magnitude of the surgical procedure was reduced (compared to those not receiving prior thrombolytic therapy) in 56 percent.
These studies demonstrate that thrombolytic therapy is a safe and effective alternative to surgery in certain subsets of patients. The Fifth ACCP Consensus Conference on Antithrombotic Therapy states that thrombolytic therapy as treatment for viable ischemia may be superior to surgical revascularization if the duration of ischemia is relatively short (less than two weeks) and there is a low risk of myonecrosis developing during the time to achieve revascularization with this method [8], while surgical therapy is superior if the length of ischemia is longer than two weeks. Although many patients treated with thrombolytic therapy will subsequently require surgical revascularization or percutaneous transluminal angioplasty (PTA), the magnitude and complexity of the procedure required to revascularize the extremity is frequently less than in those not receiving prior thrombolytics. The lower hospital mortality in the groups receiving thrombolytic therapy is probably related to avoidance of a major surgical procedure.
Thus, patients found to have an ischemic but viable extremity on clinical examination should undergo urgent arteriography in order to plan surgical or medical revascularization. There are several findings on arteriography which are used to determine if thrombolytic therapy, PTA, or surgical revascularization is the most appropriate treatment. These include:
• The presumed etiology (embolus versus thrombus)
• The location and length of the lesion
• The duration of symptoms
• The availability of autologous vein for bypass grafting
• The suitability of the patient for surgery
As an example, a proximal embolus at the bifurcation of the common femoral artery is an ideal lesion for embolectomy. On the other hand, embolus to a distal vessel (eg, to the tibial artery) may be best treated with a thrombolytic agent. The major use of PTA is in the treatment of an underlying lesion after the clot has been lysed with thrombolytic therapy.
Patients with nonviable extremities ！ Patients with nonviable extremities should undergo prompt amputation. (See "Treatment of limb threatening ischemia"). Arteriography is usually not necessary, since the level of amputation is determined by clinical findings and by the viability of tissues at the time of surgery. Every effort should be made to preserve as many joints as possible, in order to decrease the work of ambulating with a prosthesis and to improve the chances for successful rehabilitation. Delays in amputation of a nonviable extremity can result in infection, myoglobinuria, acute renal failure, and hyperkalemia.