General Review
Endovascular Management of Acute Limb Ischemia

https://doi.org/10.1016/j.avsg.2011.05.017Get rights and content

Despite major advances in pharmacologic and endovascular therapies, acute limb ischemia (ALI) continues to result in significant morbidity and mortality. The incidence of ALI may be as high as 13-17 cases per 100,000 people per year, with mortality rates approaching 18% in some series. This review will address the contemporary endovascular management of ALI encompassing pharmacologic and percutaneous interventional treatment strategies.

Introduction

Despite major advances in pharmacologic and endovascular therapies, acute limb ischemia (ALI) continues to result in significant morbidity and mortality. The incidence of ALI may be as high as 13-17 cases per 100,000 people per year, with mortality rates approaching 18% in some series.1, 2 This review will address the contemporary endovascular management of ALI encompassing pharmacologic and percutaneous interventional treatment strategies.

ALI may be defined as an acute decrease in arterial perfusion (<14 days) that threatens limb integrity and viability. ALI may result from embolic or thrombotic arterial obstruction, which in turn results in severe hypoperfusion to the distal limb (Table I). A complete evaluation, including a detailed history and physical examination, may aid in determining the etiology of the ALI (Table II). A careful examination of the affected limb with reference to the ALI classification scheme put forth by the Society of Vascular Surgery/International Society of Cardiovascular Surgery facilitates prompt and appropriate clinical management. (Table III). The critical clinical components of this assessment involved in determining the severity of extremity ALI include ischemic rest pain, pallor of the extremity, absent pulses (both by palpation and with continuous wave Doppler), presence or absence of venous Doppler signals, sensory loss, or muscle paresis. The majority of patients (45%) present with either category I or II ischemia, whereas 10% are diagnosed with a nonviable limb (category III) on initial evaluation.5 The differential diagnosis of ALI begins with the determination of thrombosis versus embolization. Emboli most frequently originate in the heart (>80%), but embolic ALI may also arise as a consequence of propagation of thrombus formed in the upstream arteries, including aneurysms or atherosclerosis of the aorta and popliteal arteries.6

Blood stasis within the left atrial appendage during atrial fibrillation and within a hyokinetic left ventricle may precipitate thrombus formation.7 Fuster et al. described arterial embolism rates of 3.5/100 patient years in 104 patients with dilated cardiomyopathy.8 Localized arterial occlusions resulting in ALI often occur within areas of preexisting atherosclerosis as a consequence of spontaneous plaque rupture. Thrombosis of lower-extremity surgical bypass grafts resulting in ALI, may be due to progressive anastomotic or graft stenosis leading to stasis and thrombus formation, or due to spontaneous prosthetic graft thrombosis. The rates of embolic ALI seem to be falling, with localized thrombosis accounting for 85% of cases in one large multicenter trial.9 Extensive acute iliofemoral deep venous thrombosis causing phlegmasia cerulea dolens (PCD) may also lead to tissue ischemia and necrosis as a consequence of the elevation of interstitial tissue pressure, culminating in impedance of capillary blood flow. Similar to ALI due to arterial disease, PCD may result in significant morbidity and mortality. Amputation and mortality rates of 12-50% and 20-41%, respectively, have been documented.10, 11 PCD is often mistaken for a primary arterial disorder; therefore, it requires prompt recognition and appropriate management to prevent limb loss.

Section snippets

Clinical Features

The severity of presenting symptoms and signs is influenced by a multitude of factors, most important of them being the extent of distal artery circulation and preexisting collateral vessels. Abrupt embolic occlusion of a previously normal lower limb arterial system without a well-developed collateral blood supply yields the sudden classic features of pain, pallor, poikilothermia, pulselessness, paresthesia, and paralysis. Localized thrombosis may result in less obvious features, particularly

Initial Management

An algorithm, outlining potential clinical management strategies for ALI is shown in Figure 1. The TASC II (Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease) guidelines recommend immediate anticoagulation with intravenous unfractionated heparin, unless a specific contraindication exists.5 However, in cases where thromboembolism is strongly suspected and a decision for immediate surgical embolectomy has been made, initiation of anticoagulation may be

Revascularization Strategy

Revascularization strategies depend on the severity of limb ischemia, as documented by the Society of Vascular Surgery/International Society of Cardiovascular Surgery criteria; lesion etiology and location; as well as the general medical status of the patient. Those patients with category I ALI are usually stable enough to enable the clinician to perform a comprehensive evaluation before developing a therapeutic strategy.

Surgical thromboembolectomy was originally described in 1963, and it was

Endovascular Revascularization

Catheter-directed thrombolysis (CDT) is an alternative to open surgery for mild-to-moderate ischemia (class I-IIa) of less than 14 days duration (class IA recommendation).13 Furthermore, CDT combined with percutaneous mechanical thrombectomy (PMT) has emerged as a therapeutic modality in those presenting with severe (class IIb) ischemia and coexistent comorbidities that may place them at a higher risk of an adverse surgical outcome. Endovascular therapy should also be considered in cases where

Arterial Access and Diagnostic Angiography

Endovascular treatment of ALI remains challenging. Satisfactory competency in basic catheter and guidewire skills, along with mastery of appropriate interventional techniques, is a vital prerequisite to the optimal management of ALI patients. To consider endovascular approaches for the patient with ALI, the operator must have all appropriate endovascular equipment readily available in the intervention laboratory so as to minimize procedural delays, incomplete revascularization, and the

Catheter-Directed Thrombolysis

The introduction of CDT over 35 years ago heralded a paradigm shift in ALI treatment.33 Current indications for CDT are summarized in Table V. Berridge et al. demonstrated higher 30-day limb salvage rates (80 vs. 45%) and significantly lower hemorrhagic complications after CDT compared with systemic intravenous delivery of recombinant tissue plasminogen activator (rt-PA) in 60 patients with ALI.35 By concentrating thrombolytic agent delivery, CDT facilitates clot dissolution and overcomes the

Adjunctive Therapy

Coadministration of unfractionated heparin is complementary to CDT and prevents pericatheter thrombosis and target-vessel rethrombosis. Clinical judgment plays a crucial role in determining the intensity of anticoagulation, as comprehensive evidence-based guidelines remain sparse. Physicians must continuously perform a risk-benefit assessment individualized to the patient during CDT. This is of vital importance as more aggressive thrombolysis and higher anticoagulation increase the likelihood

Percutaneous Mechanical and Rheolytic Thrombectomy

PMT evolved in an attempt to overcome the main limitations of CDT, namely the need for prolonged lytic infusion (with the associated increase in hemorrhagic complications) and the delay in reperfusion. Several devices, ranging from the simple aspiration-type catheters to complex RT systems composed of a drive unit, pump, and catheter, have been used (Table IX). Simple aspiration catheters (e.g., Export Catheter, Medtronic Inc., Santa Rosa, CA) typically are engineered to maximize the effective

Conclusion

Successful management of ALI remains challenging. Complex multistep revascularization strategies are required during both initial and subsequent procedures. Initial management depends on several factors, including the acuity and severity of ALI, comorbid conditions, propensity for bleeding complications, availability of operative and/or endovascular expertise, and ancillary support for the procedural care of these critically ill patients. Successful outcomes necessitate the seamless integration

References (77)

  • J.J. Earnshaw et al.

    Acute critical ischaemia of the limb: a prospective evaluation

    Eur J Vasc Surg

    (1990)
  • S. Aune et al.

    Operative mortality and long-term survival of patients operated on for acute lower limb ischaemia

    Eur J Vasc Endovasc Surg

    (1998)
  • K. Ouriel et al.

    A comparison of thrombolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia

    J Vasc Surg

    (1994)
  • S.D. LeBlang et al.

    Low-dose urokinase regimen for the treatment of lower extremity arterial and graft occlusions: experience in 132 cases

    J Vasc Interv Radiol

    (1992)
  • C.S. Cina et al.

    Intraarterial catheter-directed thrombolysis: urokinase versus tissue plasminogen activator

    Ann Vasc Surg

    (1999)
  • J. Schweizer et al.

    Comparison of tissue plasminogen activator and urokinase in the local infiltration thrombolysis of peripheral arterial occlusions

    Eur J Radiol

    (1996)
  • C.K. Shortell et al.

    Safety and efficacy of limited-dose tissue plasminogen activator in acute vascular occlusion

    J Vasc Surg

    (2001)
  • T.M. Hanover et al.

    Safety and efficacy of reteplase for the treatment of acute arterial occlusion: complexity of underlying lesion predicts outcome

    Ann Vasc Surg

    (2005)
  • K. Ouriel et al.

    Reteplase monotherapy and reteplase/abciximab combination therapy in peripheral arterial occlusive disease: results from the RELAX trial

    J Vasc Interv Radiol

    (2004)
  • M.K. Razavi et al.

    Catheter-directed thrombolytic therapy for limb ischemia: current status and controversies

    J Vasc Interv Radiol

    (2003)
  • R.D. Shlansky-Goldberg et al.

    A first-in-human phase I trial of locally delivered human plasmin for hemodialysis graft occlusion

    J Thromb Haemost

    (2008)
  • A.T. Hirsch et al.

    ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation

    J Am Coll Cardiol

    (2006)
  • J.J. Earnshaw et al.

    National Audit of Thrombolysis for Acute Leg Ischemia (NATALI): clinical factors associated with early outcome

    J Vasc Surg

    (2004)
  • J.L. Anderson et al.

    ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine

    J Am Coll Cardiol

    (2007)
  • T.P. Sarac et al.

    Clinical and economic evaluation of the trellis thrombectomy device for arterial occlusions: preliminary analysis

    J Vasc Surg

    (2004)
  • B. Davies et al.

    Acute leg ischaemia in Gloucestershire

    Br J Surg

    (1997)
  • D. Bergqvist et al.

    Auditing surgical outcome: ten years with the Swedish Vascular Registry–Swedvasc. The Steering Committee of Swedvasc

    Eur J Surg Suppl

    (1998)
  • B.T. Katzen

    Clinical diagnosis and prognosis of acute limb ischemia

    Rev Cardiovasc Med

    (2002)
  • L. Norgren et al.

    Inter-society consensus for the management of peripheral arterial disease

    Int Angiol

    (2007)
  • W.J. Manning et al.

    Accuracy of transesophageal echocardiography for identifying left atrial thrombi: a prospective, intraoperative study

    Ann Intern Med

    (1995)
  • K. Ouriel et al.

    Thrombolysis or Peripheral Arterial Surgery (TOPAS) Investigators. A comparison of recombinant urokinase with vascular surgery as initial treatment for acute arterial occlusion of the legs

    N Engl J Med

    (1998)
  • Z.K. Wlodarczyk et al.

    Low-dose intra-arterial thrombolysis in the treatment of phlegmasia caerulea dolens

    Br J Surg

    (1994)
  • D.L. Robinson et al.

    Phlegmasia cerulea dolens: treatment by pulse-spray and infusion thrombolysis

    Am J Roentgenol

    (1993)
  • S.C. Smith et al.

    AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute

    Circulation

    (2006)
  • A.T. Hirsch et al.

    ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation

    Circulation

    (2006)
  • M. Sobel et al.

    Antithrombotic therapy for peripheral artery occlusive disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition)

    Chest

    (2008)
  • D.J. Brenner et al.

    Computed tomography–an increasing source of radiation exposure

    N Engl J Med

    (2007)
  • F. Pomposelli

    Arterial imaging in patients with lower extremity ischemia and diabetes mellitus

    J Vasc Surg

    (2010)

    • Cited by (27)

    • A prothrombotic state and denser clot formation in patients following acute limb ischemia of unknown cause

      2020, Thrombosis Research
      Citation Excerpt :

      In the European population incidence of ALI is estimated at 6 to 17 per 100,000 per year and a mean age of the patients is 76 years [4,5]. Amputation rates range between 6 and 30% in 30 days and mortality reaches 9–22% at one year follow up [6,7]. The pathogenesis of ALI is complex [8].

    • Mitochondrial transplantation ameliorates acute limb ischemia

      2020, Journal of Vascular Surgery

    • Fibrinogen and catheter-directed thrombolysis

      2014, Seminars in Vascular Surgery
      Citation Excerpt :

      Additionally, newer devices, such as the Angiodynamics AngioVac, can be used to aspirate clot from the main pulmonary artery without the use of thrombolytic agents, mitigating the bleeding risk of intervention. Surgical thromboembolectomy and bypass grafting have traditionally been the preferred treatment of acute arterial thromboembolus, however, thrombolytic therapy and percutaneous transluminal angioplasty have more recently become treatment options in selected patients [181,182]. The TOPAS (Thrombolysis or Peripheral Arterial Surgery) trial, a randomized, prospective, double-blind study compared thrombolysis with surgery in patients with acute lower extremity ischemia.

    • Acute limb ischemia

      2014, Interventional Cardiology Clinics
      Citation Excerpt :

      Procedural or technical success is defined as complete or near complete (>80%) dissolution of thrombus, restoration of antegrade flow, and the absence of the need for open surgical intervention.32,33 The most powerful predictor of procedural success is the ability to position the infusion catheter within the thrombus.34 Clinical success is defined as resolution of the acute ischemic symptoms or reduction of the level of the surgical procedure or amputation.32

    • Hybrid revascularization procedures in acute limb ischemia

      2014, Annals of Vascular Surgery
      Citation Excerpt :

      Indeed, a series of 380 patients subjected to thromboembolectomy for ALI with concomitant on-table angiography revealed that almost 25% presented an underlying stenotic lesion that was subsequently treated with angioplasty.26 Interestingly, the risk of limb loss in ALI ranges from 5% to 30% with mortality rates approaching 18%.27–29 Baril et al.30 have recently reported on the outcomes of bypass procedures, performed for ALI in a series of 323 patients.

    • Isquemia aguda de las extremidades

      2013, Medicine (Spain)
    View all citing articles on Scopus
    View full text
    Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier B.V. All rights reserved.