I. Definition and etiology Acute Limb Ischemia (ALI) is a sudden reduction in limb perfusion due to any etiology and potentially endangers limb viability. In contrast to Chronic Critical Limb Ischemia (CLI), the duration of ALI does not exceed 2 weeks. The duration of symptoms is related to the severity of the ischemia and the early or late access to medical care. There are many causes of ALI (see Table I), including reconstruction/graft thrombosis, embolism, autologous artery thrombosis, peripheral aneurysm appendage thrombosis/thrombosis, and trauma (including medical origin), with graft thrombosis being the most common cause of ALI. The severity of symptoms is related to the cause, with embolism, peripheral aneurysm appendage thrombosis/thrombosis, and trauma being the most common causes of sudden onset of severe pain in the early stages (within a few hours), and graft or autologous artery thrombosis in the later stages (several days). The early onset of symptoms is related to the amount of collateral circulation or whether thrombus prolongation involves important collateral branches causing outflow tract obstruction. Cheng Wei, Department of Vascular Surgery, Beijing Anzhen Hospital Compared with other diseases of vascular surgery/endovascular surgery, the prognosis of ALI is still not optimistic, and it is important to investigate the reasons for this and to recognize and deal with it correctly. Clinical manifestations 1. The general clinical manifestations of ALI are mostly summarized as 5Ps or 6Ps: pain (pain), pulselessness (puleslessness), pallor (pallor), abnormal sensation (paresthesia), paralysis (paralysis) and skin temperature change (poikilothemia). The time of first onset, location, degree of pain and changes in the location and degree of pain over time should be understood. Pulselessness: Loss of foot arterial pulsation suggests but does not confirm the diagnosis of ALI, nor does palpation exclude ALI. bedside ankle arterial pressure measurements are highly informative, and the absence of foot flow signal by Doppler is highly correlated with the diagnosis of ALI. tASC-II (Trans-Atlantic Intrer-Society Consensus Document on Management of Peripheral Arterial Discase, TASC) recommendation #29 emphasizes that all patients with suspected ALI should be evaluated immediately with Doppler for the presence of a flow signal due to inaccurate pulse and physical examination [C]. Pallor: Compared to the healthy side, ALI generally has local color and temperature changes and slow or deflated venous filling. More than half of the patients have hypesthesia, and paresthesia is a sign of advanced disease. 2, Etiology and clinical manifestations Although ALI all emphasize 5Ps or 6Ps, the clinical manifestations vary by etiology. This aspect can be categorized as acute arterial embolism, acute arterial thrombosis and ALI due to trauma. Acute arterial embolism has an acute onset with severe pain, mostly occurring suddenly during activity, and the pain plane shifts downward with time. Acute arterial embolism is located in a relatively healthy vessel with no significant collateral circulation, so the risk of permanent injury may arise after 6h-8h of onset. These patients often have a history of atrial fibrillation, old infarction, or upstream arterial aneurysm. Emboli are primarily of cardiac origin and nowadays are mainly due to atherosclerotic heart disease. Thrombosis on the basis of arterial stenosis is mild or insignificant in these patients, and the time of onset is often inaccurately stated. Patients have very pronounced sensory abnormalities and often have intermittent claudication, PTA/PCTA, presence of atherosclerotic risk factors (advanced age, hypertension, diabetes, smoking), stroke, hypercoagulable conditions, and history of amputation. Since thrombosis is the most common cause of ALI, the new monograph “5Ps/6Ps” ranking has sensory abnormalities as the first symptom [2]. ALI due to trauma, most often seen in compound injuries, is easily missed due to masking by other systemic injuries or inexperience. For example, lower middle femur fractures, tibial plateau fractures, and knee dislocations are easily combined with arterial injuries, which can be disrupted vascular continuity, partial disruption, or simple endothelial entrapment, intermural hematoma compressing the true lumen, or endothelial inversion. Medically induced ALI is often not in the specialty in the first instance and can also be easily misdiagnosed. Evaluation of the degree of ischemia The degree of limb ischemia is mainly based on the presence of resting pain, sensory loss or motor deficits. The SVS (The Society for Vascular Surgery) and TASC-II advocate the Rutherford Criteria (see Table II) to evaluate the degree of ischemia in ALI. The Rutherford Criteria is divided into three types [3]. Type I: Limb viability is present and treated with elective management/conservative treatment. Type II: limb viability is threatened and requires revascularization to preserve the limb. Type III: the limb is in an irreversible ischemic state. After revision, type II is further divided into IIa and IIb. IIa means that limb viability is not immediately threatened (within days to weeks); IIb means that limb viability is severely threatened and should be urgently (within hours) revascularized to preserve the limb. Diagnosis and differential diagnosis of ALI includes three elements: 1. the presence or absence of a disease that resembles ALI 2.The presence of non-ASO etiology. 3. Among the atherosclerotic etiologies, it is embolism or thrombosis that causes ALI. Etiology of ALI or cool ALI etiology (see Table III). Arterial injury or entrapment Obvious arterial injury is easy to diagnose, and arterial injury in compound injury is easy to miss, so for fracture or joint dislocation at specific sites, downstream arterial pulsation and bedside Doppler examination should be routinely checked. Medical-derived arterial injuries are also easy to overlook. Patients who have recently received invasive diagnosis or treatment and present with femoral artery obstruction should be alerted to the possibility of medical-derived injury. Aortic entrapment tearing downward may involve the abdominal aorta and iliac artery. Hypertension with sudden onset of severe tearing-like pain in the interscapular region or back is a clear indication of acute aortic entrapment. Acute iliac artery obstruction should be considered as a possible entrapment. Ergot poisoning Ergot poisoning causing ALI is rare and can involve any part of the artery and cause thrombosis, but rarely immediately endangers limb viability. HIV arteriopathy Patients with severe immunosuppression and a CD4 count below 250/cm3 may develop ALI, which is associated with acute and chronic cellular infiltration of the trophoblast in the vessel wall of the limb and viral proteins in the lymphocytes. The primary management includes embolization, diversion and thrombolysis. There is a high rate of reocclusion and amputation. ALI is generally more severe, and N artery distress is usually seen in younger people, whereas epicardial cystic degeneration is seen in older people. The diagnosis can be confirmed by ultrasound or CTA. N aneurysms with thrombosis are often diagnosed as acute arterial embolism. A complete filling of the aneurysm with thrombus or repeated “junk legs” can cause an ALI. 50％ N aneurysms are bilateral and the femoral artery is often dilated, and ultrasound can quickly clarify the diagnosis. Thromboembolism Most often seen in patients with atrial arrhythmias, old heart attacks, congestive heart failure, and heart valve disease. Atrial septal or ventricular septal defects with concomitant venous thrombosis can also cause arterial embolism. Patients often have a history of interstitial claudication. Arteriograms show multiple filling defects, a “curved moon” sign at the proximal end of the embolus, and few or no side branches. Arterial thrombosis These patients often have localized atherosclerotic stenosis. Characterized by relatively slow onset, numbness may be a prominent complaint, and intermittent claudication and risk factors for atherosclerosis are often present. In addition to general examination and necessary important organ function examination, ALI mainly emphasizes on imaging examination, color Doppler is one of the most common examinations, DSA, CT and MRA are also frequently used. The patient should be evaluated before the examination to see if he/she can tolerate or has time to allow for the relevant tests. V. Treatment of ALI The initial goal of treatment of ALI is to prevent prolongation of thrombus and aggravation of ischemia. Therefore, heparin sodium anticoagulation should be performed immediately. After diagnosis, there are two main types of treatment: intracavitary treatment and surgical treatment. Although there is insufficient evidence to support which category is better for limb preservation or mortality within 30 days, there is an emerging consensus that improving circulation takes precedence over preserving distant patency.Bergqvist et al [4] summarized the trend in treatment options for ALI in Sweden from 1984 to 2007, with the choice of open surgery for acute arterial embolism decreasing each year and the choice of endoluminal surgery increasing each year; acute arterial thrombosis is more often treated with endoluminal Endoluminal therapy is more often chosen for acute arterial thrombosis. Endoluminal therapy The main component of endoluminal therapy for ALI: catheter-directed thrombolysis (CDT), and other advances in this field are centered on how to make local thrombolysis faster to restore circulation and safer. Systemic thrombolysis has no place in the treatment of ALI. CDT is performed under local anesthesia by puncturing through the contralateral femoral artery (or brachial artery in special cases) and turning the hill to deliver a multilaterally perforated thrombolytic catheter (unifuse infusion system) to the lesioned segment. Dissolution of the thrombus is achieved by continuous low-pressure infusion of thrombolytic agent. The commonly used thrombolytic agents are urokinase, recombinant tissue-type fibrinogen activator and streptokinase, of which urokinase is the most commonly used. During the thrombolytic period, anticoagulation is appropriate, and sodium heparin 200-500 U/h is pumped continuously. During thrombolysis, maintain APTT at 2-2.5 times normal and plasma Fib ≥1.5 g/L. For patients with hypoproteinemia, thrombolytic agent dosage should be started from the low limit, and the cause of significantly reduced Hb should be investigated and treated accordingly. Contraindications to thrombolysis should be noted before thrombolytic therapy (see Table IV). The indication of CDT for ALI is mainly applicable to patients with ischemia degree in type I – IIa. With the improvement of devices and techniques that allow removal of thrombus in a shorter period of time, some more severe ischemia is also treated with CDT. There are more than a dozen brands of devices in this area (see Table V), which are divided into two main categories: “aspiration” or “microfragmentation-only” in terms of function, and are collectively classified as mechanical clot removal, due to the presence of Due to the risk of distal “trash leg” and injury, only the Trellis System and Angiojet System are approved for peripheral vascular use. Trellis System: Once the Trellis System catheter is in place, the balloons at each end of the Trellis catheter are opened to isolate the thrombus from the circulation before thrombolysis begins. A special oscillating wire accelerates the flow of the thrombolytic agent through the isolated segment of the vessel, and the thrombus fragments are finally aspirated out of the body. The advantages of this system are fast thrombolysis, low dosage of thrombolytic agent, few complications and low chance of outflow tract embolism [5]. Angiojet System: this is done with the help of a negative pressure zone formed around a high-speed jet of fluid, into which the thrombus falls and is broken up and sucked out of the body. A retrospective study concluded that Angiojet + adjuvant CDT should be the first choice for the treatment of ALI. In conclusion, CDT as the core, together with the application of adjuvant devices, can correct acute ischemia in a minimally invasive and rapid manner; and the local anatomical factors that cause ALI (e.g., stenosis, ulceration, anastomotic obstruction) shown after thrombolysis can be selected as an emergency or elective, intraluminal or open treatment option depending on the patient’s systemic condition and medical condition. the advantages of CDT have been demonstrated by three major randomized controlled studies ( Rochester, STILE and TOPAS). The CDT group had lower amputation and mortality rates than the open surgery group. For this reason, TASC-II recommends CDT as the “initial” treatment option for ALI. Open treatment The indications and methods for open treatment of ALI are well established. However, in acute cases, the poor general condition of the patient and the hasty preparation make the perioperative mortality and amputation rate of open surgery high. As the concept of “hybrid procedure” and the priority of improving circulation over patency is gradually recognized. The emphasis on “time window” in traditional surgery has been gradually reduced. However, open surgery is preferred for some ALIs, such as acute injuries, especially in the case of compound injuries; N aneurysm thrombosis in a patent outflow tract; and extra-anatomic bypass graft obstruction above the groin (outflow tract end-to-end anastomosis). The choice of open management for ALI due to non-traumatic causes should take into account contraindications and the timing of surgery. Before the end of open surgery, unless there is sufficient evidence that appropriate circulation has been restored, angiography or ultrasonography should be routinely performed to prevent residual lesions. Amputation Ischemic degree type III, with the exception of very few (ischemic time <3h), advocates one-stage amputation, with the amputation plane usually above the knee (accounting for 80％). Postoperative management Fascial compartment dissection and decompression: after successful restoration of blood flow in patients with ALI, fascial compartment dissection is roughly 5.3％, with an incidence of up to 25％ in tertiary hospitals. Fascial compartment syndrome presents with pain, edema, and sensory abnormalities that are disproportionate to local signs. A fascial compartment pressure of ≥20 mmHg is an indication for dissection, and all four fascial compartments should be adequately dissected and decompressed. The tibial nerve travels in the deep posterior compartment, and failure to decompress this compartment (which is easily missed) may result in severe functional impairment of the affected limb. Transverse myelolysis: Myoglobin is detected in the urine of patients with ALI at a rate of up to 20％. Acute renal failure occurs in half of patients with creatine kinase over 5000 units/L. Urinary myoglobin > 1142 nmol/l (> 20 mg/dl) suggests acute renal failure, and rhabdomyolysis is manifested as teichromaturia, elevated serum creatine kinase or positive urinary myoglobin. Treatment is mainly adequate hydration, alkalinization of the urine and elimination of the source of myoglobin. The benefit of mannitol and plasma replacement (plasmapheresis) has not been found. VI. Clinical outcomes and outpatient follow-up ALI mortality rates are in the range of 15-20％ , with major complications being hemorrhage. Major amputations are up to 25％ , fascial compartment dissection rates are 5-25％ and renal insufficiency is up to 20％ , and the foot Doppler flow signal or ABI should be routinely reviewed postoperatively. Heparin anticoagulation is applied perioperatively, warfarin is renewed for 3-6 months, and long-term anticoagulation is indicated for arterial thromboembolism, which has a high chance of postoperative recurrent limb ischemia in randomized controlled studies. Those who cannot adhere to long-term anticoagulation (e.g., bleeding) should consider antiplatelet therapy. The source of the embolus, cardiogenic or arterial, should be sought after surgery, but the source of the embolus cannot be traced in many patients. VII. Prospects of ALI With the gradual recognition of the concept of hybrid disposition and the priority of improving circulation over the pursuit of distant patency, the treatment strategy for ALI is moving toward, and should be, CDT to dissolve fresh thrombus - dealing with lesions obscured by thrombus. The application of effusion tract protection umbrella becomes part of the treatment. New thrombolytic agents, which may make thrombolysis more effective and convenient.