No immediate limb threat
Salvageable if treated promptly
Salvageable if treated immediately
More than just toes
Limb loss or permanent damage
The acute limb ischemia symptoms are memorized by the six P’s: Pain, Pallor, Paresthesia, Paralysis, Pulseless, and Poikilothermia. Laboratory tests are used to quantify both local and systemic impairment. Muscle necrosis leads to increase in creatine phosphokinase levels. Furthermore, leukocytosis, metabolic acidosis, hemoconcentration, and impairment of renal function may be present .
Imaging exams such as duplex scan, computerized tomography, magnet resonance angiography, and digital subtraction angiography are not required for diagnosis. They are useful in atypical presentation or in doubtful situations and should be done for anatomical details and revascularization planning, if the patient can wait due to the ischemia severity [15, 22].
Arterial Duplex Scan helps to identify the level of occlusion, checking also the patency of other distal arteries, which may be useful in surgical planning. It may suggest the age of the thrombus as well by its echogenicity. It also can diagnose thrombosed aneurysm as the cause of ischemia. It is a fast and cheap method that can be used at bedside and is very accurate before and after intervention .
Arteriography defines the site of obstruction, the quality of the distal arteries, the concomitant presence of atherosclerotic disease, and collateral circulation, obtaining relevant data for surgical planning and technique adoption. It may be performed intraoperatively .
Other imaging methods such as computed tomography angiography and magnetic resonance angiography can be useful, but is time-consuming and may delay the treatment leading to bad outcome. Therapy delay may be determinant for limb loss and death .
Echocardiography is useful in identifying potential embolic sources, but it is not essential for diagnosis or for the revascularization procedure [3, 4].
Other conditions that may mimic acute limb ischemia are: hemodynamic shock, phlegmasia cerulea dolens, acute compressive neuropathy, aortic dissection, ergotism, HIV’s arteriopathy, compartmental syndrome, and vasculitis. In these patients, imaging exams help to elucidate the diagnosis [1, 15, 24–27].
Initial treatment aims to prevent thrombus’s progression and relies on systemic anticoagulation. Best initial choice is continuous intravenous infusion of unfractioned heparin, keeping activated partial thromboplastin time between two and three times above the baseline time . Direct thrombin inhibitors may be used if heparin is not possible, but they are not approved by the US Food and Drug Administration (FDA) for this propose. It is indicated in reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation .
All patients with suspected acute limb ischemia should be immediately evaluated by a vascular specialist, especially when neurological symptoms are present, particularly muscle weakness. Waste of time can lead to limb damage, sometimes irreversible. The surgeon will define the need and timing of revascularization and which way should be the best approach: open or endovascular surgery [29, 30].
There are two endovascular techniques for flow restoration on patients with acute limb ischemia: catheter-directed thrombolysis and mechanical thrombectomy .
Catheter-directed thrombolysis is intra-thrombus infusion of thrombolytic drugs through a multi-perforated catheter. The clot dissolution is slow and may take more than 24 h. Therefore, it should not be used in advanced ischemia, i.e., with loss of motor function, where immediate reperfusion is mandatory. It is indicated for the categories I and IIa patients, with better results if accomplished preferably in the first 15 days. It carries increased risk of bleeding due to thrombolytic drugs use. Thrombolytic agents include streptokinase, urokinase, pro-urokinase, and recombinant tissue plasminogen activators [32–34].
The mechanical thrombectomy devices are endovascular catheters able to promote immediate clot lysis [2, 31]. The mechanism of action consists of mechanical thrombi’s fragmentation, followed by aspiration and removal, quickly reestablishing blood flow. Some devices allow the injection of a thrombolytic agent, under pressure, into the thrombi, which is called pharmaco-mechanical thrombolysis . This aims to accelerate the dissolution of the thrombus with a lower dose of thrombolytic agents, in order to decrease the risk of bleeding. Mechanical thrombectomy, contrary to catheter-directed thrombolysis, can be used in selected patients with advanced ischemia, i.e., when muscle weakness is already established [31, 35, 36].
After thrombus dissolution, completion angiography is mandatory to investigate and identify the unstable injury that caused the occlusion. The endovascular approach allows correction of these lesions, by angioplasty, with or without stent, at the same procedure .
Conventional Open Surgery
Open surgery is more appropriate for patients with embolic occlusion and/or for those with aortoiliac involvement. In the event of failure of the endovascular therapy, open surgery may still be an option [3, 4]. Conventional surgery can be done by two ways: thromboembolectomy and/or arterial bypass.
The first consists of thrombus extraction with a catheter with a balloon at its end—embolectomy catheter (Fogarty catheter). Arteriotomy is performed near the site of occlusion; the catheter is introduced, under direct vision and, when the catheter reaches the distal arterial segment, the balloon is inflated and pulled back, dislodging and bringing out the thrombi. This technique is the first choice for patients with embolic acute limb ischemia and for those with previous bypass or angioplasty occlusion .
The second method, arterial bypass, has been described before and follows the same principles for peripheral arterial disease patients. It is performed when thromboembolectomy fails, inadequate removal of thrombi, or insufficient flow restoration . It is very useful for peripheral aneurysm occlusion repair .
In situations of irreversible damaged limb (acute limb ischemia class III patients), the best treatment choice is primary amputation at a proper level. Attempt to revascularize such patients can trigger severe inflammatory and metabolic responses, due to reperfusion syndrome , adding high rates of morbidity and mortality [9, 30].
Syndrome of Reperfusion
The most feared complication of revascularization is reperfusion syndrome , and its severity is closely associated with the intensity of ischemia and its duration. Systemic and regional metabolic changes are triggered by rhabdomyolysis. It is characterized by metabolic acidosis, hyperkalemia, increased creatine phosphokinase serum level, increased blood partial pressure of CO2, decreased blood partial pressure of O2, and myoglobinuria, leading to myocardial depression, respiratory failure, and acute renal failure. If untreated, can lead quickly to death [21, 42, 43].
Muscle compartment syndrome occurs, due to severe swelling of the muscles inside the inextensible muscle fascia after revascularization, increasing the pressure inside this compartment. If the pressure equals or exceeds the diastolic pressure, muscle perfusion is jeopardized and ischemia installs. The treatment of compartment syndrome is through fasciotomy, a long longitudinal surgical opening of muscular fascia for decompression [44–46].
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