The most effective method to treat acute arterial embolism of the lower extremity is to remove the embolus with a Fogarty catheter by incising the artery, however, the presence and displacement of residual thrombus or incomplete recovery of perfusion due to combined atherosclerotic stenosis occlusion makes the effect of embolus removal not very satisfactory. However, the presence of residual thrombus and the incomplete recovery of perfusion due to the occlusion of combined atherosclerotic stenosis make the results of thrombus extraction unsatisfactory. In this paper, we retrospectively summarize the common hybridization strategies used in the treatment of acute arterial embolism in the lower extremities. [Keywords] Hybrid surgery; acute lower extremity arterial embolism; incisional artery retrieval; endoluminal intervention; thrombolysis. The hybrid therapeutic strategies for acute lower extremity arterial embolism WANG Bing, LI Jian-lin, WANG Yue, CUI Wenjun, ZHAO Lei, LI Yang, LI Panfeng Deparment of Vascular Surgery, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China 【Abstract】 The most efficient treatment for acute lower extremity arterial embolism treatment for acute lower extremity arterial embolism is operative thromboembolectomy with Fogarty’s balloon catheter, but the incomplete restoration of perfusion which lead to poor clinical outcome because existence and propagation of residual thrombi or presence of underlying atherosclerotic steno-occlusive lesions, the hybrid therapeutic strategies may be a solution to this problem. the combination of surgical and The combination of surgical and endovascular options may overcome the limitations that characterize the traditional approachs, this review article summarizes the common hybrid Key words】 Hybrid surgery; acute lower extremity arterial embolism; operative Acute arterial embolism is an acute occlusion of an extremity artery caused by dislodged emboli or local thrombosis. The common sources of emboli are cardiogenic (atrial fibrillation, myocardial infarction, rheumatic heart disease, artificial heart valve, bacterial endocarditis or atrial mucinous aneurysm, etc.) and vascular origin (atherosclerosis, aneurysm, artificial intravascular thrombus, intra-arterial manipulation and intra-arterial foreign body, etc.). Acute arterial embolism due to rheumatic vascular disease and atrial fibrillation has gradually decreased in recent years, while embolism on the basis of atherosclerosis and more complex disease patterns have gradually increased in patients. This article provides a review of the treatment strategies for acute arterial embolism of the complex lower extremity. 1 Treatment of acute arterial embolism 1.1 Surgical dissection of the artery to remove the embolus There are three main approaches to the treatment of early acute arterial embolism: (1) attempting to remove the embolus and thrombus; (2) removing as much of the thrombus and embolus as possible, however with tools not specifically designed for thrombus removal; and (3) amputation. A truly effective treatment emerged with the invention of the “Fogarty” thrombectomy catheter by Thomas J. Fogarty in the 1960s [1]. Since then, surgical thrombectomy has been considered the most effective treatment for acute arterial embolism for many years, especially when the embolism involves only one large artery of the lower extremity. 1.2 Intraluminal interventional thrombolytic therapy In 1970, a less invasive approach emerged – intra-arterial thrombolytic therapy [2]. The principle of direct thrombolysis by arterial catheter is the activation of fibrinolytic enzymes, and the activated fibrinolytic enzymes are able to dissolve pathological thrombi. Intracatheter infusion of thrombolytic agents not only increases the local concentration of fibrinolytic enzymes and improves the chances of thrombus lysis, but also prevents the local fibrinolytic enzymes of the thrombus from being neutralized by circulating antagonists, so that effective thrombus lysis can be achieved with a smaller dose. 2 Hybrid surgery for acute arterial embolism of the lower extremity Surgical techniques have improved considerably in the last few years and perioperative monitoring has been enhanced, however, the results of thrombus retrieval are still not very satisfactory, with Braithwaite et al. reporting a 30-day mortality rate of 42% [3] and available data reporting a 5-year survival rate of only 17%-44% [4-5], which may be related to incomplete recovery of perfusion (e.g., thrombus in the end vessel that cannot be reached by the thrombolytic catheter, the presence and displacement of residual thrombus, combined atherosclerotic disease, or even vascular injury caused by the passage of the thrombolytic catheter). Despite the many theoretical advantages of less invasive endoluminal thrombolysis, there are insufficient data to confirm its superiority over surgical angioplasty [6], and data published in 2000 showed no significant difference in amputation and mortality rates between endoluminal thrombolysis and surgical treatment [7]. Plecha et al. performed angiography during arterial thrombectomy to assess post-thrombectomy patency and lumen condition (presence of potential vascular damage) and found residual thrombus in the terminal arteries and arteries not reached by the thrombectomy catheter in 36% of patients [8], using intravascular fiberoptic endoscopy The technique demonstrated residual thrombus and appendage thrombus in the lumen after embolization in 82% of patients [9]. Intraoperative angiography supplemented with endoluminal intervention is considered the most reliable method to ensure complete restoration of perfusion in major arteries and their branches [10]. Intraoperative adjunctive endoluminal interventions to compensate for the lack of surgical treatment to complete the treatment, will be the most used technique by vascular surgeons in dedicated hybrid operating rooms in the future. 2.1 Surgical + endoluminal intervention (type I hybridization mode for acute lower extremity arterial embolism) In patients with acute arterial embolism, an incisional fogarty catheter is used to retrieve the embolus (Figure 1), and different types of catheters are used to retrieve the embolus in a cascade and retrograde fashion, so that the thrombus is removed as much as possible, resulting in good spurting and regurgitation. Intraoperative arterial angiography was performed (Figure 3) to assess the vascular condition and observe the presence of unretrieved thrombus, its location and local anatomical factors. In case of residual thrombus, a super-selective fogarty catheter can be used for thrombus extraction under X-ray fluoroscopy (due to the lack of curvature at the tip of the fogarty catheter, such super-selective arterial thrombus extraction requires a high level of operator skill and familiarity with vascular anatomical factors, and further experience and practice are needed, Figure 4), and/or thrombus can be removed as much as possible using thrombus aspiration techniques. The distal and proximal ends are contrasted using a superselective guidewire catheter technique, and balloon dilation and/or stenting is performed if necessary (Figure 5). Zaraca et al. demonstrated that routine intraoperative angiography after thrombus removal reveals more vascular damage than selective angiography also necessitates more endoluminal interventional adjuncts (i.e., hybridization), which also has a better prognosis and a lower rate of restenosis at 24 months [11]. Intraoperative angiography not only determines the need for endoluminal interventions but also guides their treatment, such as angioplasty and stenting, which can be performed immediately after embolization and thus simplifies and accelerates treatment. 2.2 Surgical + thrombolytic therapy (type II hybrid approach for acute arterial embolism of the lower extremity) The judicious use of thrombolytic agents during surgical embolization can lyse the residual thrombus in the embolized artery along with the displaced thrombus and the thrombus in the branch vessels that cannot be reached by the embolization catheter. Parent et al. found intra-arterial infusion of fibrinogen activator in patients with residual thrombus in the N artery after intraoperative angiography and showed successful thrombus lysis in 88% of patients after a 30 min delay in reimaging [13]. Many scholars are concerned that intraoperative intra-arterial infusion of thrombolytic agents increases the risk of bleeding. In fact, with local infusion of thrombolytic drugs using an arterial catheter, few, if any, fibrinogen activators or fibrinolytic enzymes enter the circulatory system, and even if a limited amount enters the circulatory system, it will be rapidly neutralized by circulating antagonists without causing systemic effects. A multicenter, randomized, blinded, and placebo-controlled trial confirmed that intraoperative thrombolytic therapy is safe and does not increase bleeding-related complications, and recommended the use of mega-dose thrombolytic therapy for acute embolism of multiple vessels with residual intractable thrombus and dislodged emboli in the limb, as single or even double doses of intra-arterial thrombolytic drugs are often insufficient. Patients who received intraoperative urokinase had a higher postoperative survival rate than those who received placebo [14]. The choice of thrombolytic therapy depends on many factors, such as the location of the lesion, anatomical factors, duration of occlusion, patient risk factors (coexisting disease) and risks associated with the operative procedure [15-17]. Most of the emboli that abscond to the femur are old thrombi that have been in the original organ of embolization for a long time, and such emboli are not as sensitive to thrombolytic enzymes as thrombi that have formed recently at the embolization site. Contraindications related to thrombolysis must be fully considered. 2.3 Thrombolysis + endoluminal intervention (combined type III approach for acute arterial embolism of the lower extremity) Current thrombolytic catheter thrombolytic techniques include various specific fibrinolytic drugs and multiple local infusion modalities (pulsed jet, intra-thrombotic high-dose drug technique). McNamara et al. concluded that the best treatment for acute arterial embolism is thrombolysis, especially if the guidewire can be successfully passed through the occluded segment [18]. If the guidewire cannot pass through the occluded segment, a period of thrombolytic therapy may be interspersed, and failure of the guidewire to pass after a period of thrombolytic therapy may indicate a relatively poor outcome [19-20]. Even if a thrombolytic catheter is successfully placed, repeated imaging should be performed during thrombolysis to clarify the vascular alignment and lesion area. If the imaging shows underlying arterial restrictive damage (atherosclerotic stenosis or intimal damage), although it rarely causes acute arterial embolism or severe limb ischemic symptoms, these factors may increase thrombosis and should be addressed as well. Mechanical thrombus removal devices use a saline spray with a venturi effect to continuously agitate the thrombus locally (considered a “vortex of water”), thus selectively capturing, dissolving and evacuating the thrombus. The effectiveness of removal depends mainly on the nature of the thrombus (fresh thrombus is more effective than old thrombus), an external suction device or a high-speed rotating impeller is attached to remove the thrombus, and a rotating and hydraulic recirculation device can shorten the time of intraluminal treatment with thrombolytic drugs, which also reduces bleeding-related complications, but its use is still limited and restricted to small vessels [21-23]. The percutaneous aspiration thrombectomy technique involves the use of a larger diameter catheter connected to a negative pressure syringe to aspirate the intravascular thrombus [24].Wagner et al. used the percutaneous aspiration thrombectomy technique to revascularize and perfuse 86% of patients [25]. Percutaneous aspiration thrombectomy is a typical adjunct to thrombolytic therapy or is used as a remedial treatment for terminal thrombi that have not been completely removed surgically. Mechanical thrombus removal and percutaneous thrombus removal techniques can improve the short- and long-term efficacy of intra-arterial thrombolysis, helping to achieve two important clinical outcomes: combined thrombolysis for removal of insoluble material or extrusion of the thrombus to accelerate the return of perfusion, and for correction of vascular damage caused by the thrombolytic process or manipulation. CONCLUSION: Intraoperative angiography can guide the treatment of open vascular surgery and can facilitate and improve many aspects of its operational standards. Correspondingly, open surgery can facilitate the operation of many endoluminal interventions. It is becoming increasingly important to be familiar with both open surgical and luminal interventional techniques to treat acute atheroembolic disease with an optimal modality. The current treatment paradigm for patients with acute arterial embolism should include both open surgery and luminal interventions, i.e., hybrid surgical treatment, with improvements in technology making treatment increasingly easier and safer. For a specific clinical situation, multiple alternative treatment strategies have the potential to reduce the morbidity and mortality previously associated with vascular occlusion. The best outcome for patients with acute lower extremity arterial embolism should be prompt recognition of the disease and immediate and rapid standardized treatment in order to minimize the risk of amputation and subsequent reperfusion injury. References: [1] Fogarty TJ, Cranley JJ, Krause RJ, et all. A method for extraction of arterial emboli and thrombi [J]. 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