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Diagnosis and treatment of acute limb ischemia

Based on the Inter-Society Consensus Edited by Mark R Nehler MD, Associate Professor of Surgery University of Colorado Health Sciences Center, Denver, CO, USA
Supported by an educational grant from Mitsubishi Tanabe Pharma Corporation. Mitsubishi Tanabe Pharma Corporation was not involved in the development of this pocket guide and in no way influenced its contents.

CONTENTS
Introduction Acute limb ischemia denition and nomenclature Evaluation
History Present illness Past history Physical examination Clinical classication of acute limb ischemia Differential diagnosis of acute limb ischemia Investigations for acute limb ischemia

4 5 6 6 7 7 8 9 11 13 14 15 15 18 18 19 19 21 21 21 22 23 3

Treatment of acute limb ischemia

Endovascular procedures for acute limb ischemia Pharmacologic thrombolysis Surgery Amputation Immediate post-procedural issues Reperfusion injury: compartment syndrome

Clinical outcomes
Systemic/limb Follow-up care

Key points therapeutic options References

Introduction
Acute limb ischemia (ALI) is a serious medical condition characterized by a rapid decrease in limb perfusion. It usually produces new or worsening symptoms or signs, and often threatens limb viability. ALI is a sequela
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Acute limb ischemia definition and nomenclature

ALI is dened as a sudden decrease in limb perfusion that could threaten limb viability. ALI has different etiologies (Figure 1). Timing of presentation is related to ischemia severity1: Patients with embolism, trauma, peripheral aneurysms and emboli tend to present early (within hours) due to lack of collaterals and/or extension of thrombus to arterial outow Later presentations (within days) tend to be restricted to those with native thrombosis or reconstruction occlusion ALI may be the rst manifestation of arterial disease in a previously asymptomatic patient or may occur as an acute event that causes symptomatic deterioration in a patient with antecedent lower extremity PAD and intermittent claudication3

of peripheral artery disease (PAD). There are diverse etiologies for ALI, with the two most common being embolus and thrombosis in situ secondary to underlying disease such as atherosclerosis. The 30-day mortality and amputation rates are 15% and up to 2530%, respectively. Outcomes and prognosis of ALI largely depend on the rapid diagnosis and initiation of appropriate and effective therapy. General practitioners
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can play a key role in this respect, by providing an early and accurate diagnosis. In this pocket guide, the diagnosis and treatment of ALI will be discussed. ALI is associated with a high amputation and mortality rate

Figure 1. Etiology of acute limb ischemia4,5

Present illness
Leg symptoms in ALI relate primarily to pain or limb function. The abruptness and time of onset of the pain, its location and intensity, as well as change in severity over time should all be explored. The duration and intensity of the pain and presence of motor or sensory changes are very important

Reconstruction/graft thrombosis Trauma (including iatrogenic) Native thrombosis

Embolism Peripheral aneurysm with embolus or thrombosis

in clinical decision-making and urgency of revascularization.

Evaluation
An accurate and thorough initial examination is of prime importance for effective diagnosis and therapeutic management of patients with ALI.

Past history
It is important to ask whether the patient has previously had: Leg pain (e.g. a history of claudication) Interventions for poor circulation A diagnosis of heart disease (e.g. atrial brillation) or aneurysms (i.e. possible embolic sources) Patients should also be asked about serious concurrent disease or atherosclerotic risk factors, including: Hypertension Diabetes Smoking 7

History
The history should have two primary aims: 1. Querying leg symptoms relative to the presence, onset and severity of limb ischemia (present illness) 2. Obtaining background information (e.g. history of claudication, recent intervention on the proximal arteries or diagnostic cardiac catheterization), pertaining to etiology, differential diagnosis and 6 the presence of significant concurrent disease

Hyperlipidemia Whether they have a family history of: Cardiovascular disease Strokes Blood clots Amputations

Paresthesia: approximately half of patients experience some form of numbness Paralysis: this is a very signicant indicator that the patient has a poor overall prognosis Doppler analysis involves the use of an ultrasound scanner to assess blood ow velocity. It can be used to measure a patients ABI and segmental limb pressure

Physical examination
Patients with ALI may initially present with the following ve symptoms, known as the 5 Ps: Pain: variables include time of onset, change over time, location and intensity Pulselessness: the absence of pedal pulses suggests that the patient has ALI. However, the patients ankle-brachial index (ABI) should be measured immediately to conrm the diagnosis. An absent Doppler ow signal in the arteries of the feet is indicative of ALI Pallor: patients with ALI commonly experience 8 changes in color and temperature

Clinical classication of acute limb ischemia

The severity of ALI is the main consideration that dictates the initial treatment received by the patient. The three factors that are used to dene the severity of the patients condition, and hence whether the patient is suitable for revascularization, are: The presence of rest pain Sensory loss Muscle weakness 9

Muscle rigor, tenderness or ndings of pain with passive movement are indicative symptoms of advanced ALI. A number of different categories are used to identify each stage of ALI, including the sensory loss and muscle weakness symptoms experienced by the patient (Table 1). The frequency of different categories of ALI on presentation is shown in Figure 2.
Table 1. Separation of threatened from viable extremities6
Findings Category Description/ prognosis Sensory loss I. Viable Not immediately threatened None Muscle weakness None

Figure 2. Categories of ALI on presentation1

Category I Viable

Category II Threatened

Category III Nonviable*

Data presented summarize both registry and clinical trial data *Some of these patients are moribund

Differential diagnosis of acute limb ischemia

There are three levels of differential diagnosis in ALI: 1. 2. Is there a condition mimicking arterial occlusion? Are there other nonatherosclerotic causes of arterial occlusion present and, if not, 3. Is the ischemia caused by an arterial thrombosis or embolus? The conditions that can cause or mimic acute arterial
Profound, paralysis (rigor)

IIa. Marginally threatened

Salvageable if promptly treated

Minimal (toes) or none

None

IIa. Immediately threatened

Salvageable with immediate revascularization Major tissue loss or permanent nerve damage inevitable

More than toes, associated with rest pain Profound, anesthetic

Mild, moderate

III. Irreversible

occlusion are listed in Table 2.

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Reproduced with permission

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Table 2. Differential diagnosis of ALI1

Investigations for acute limb ischemia

Routine laboratory studies should be obtained in patients with ALI:

Conditions mimicking acute limb ischemia: Systemic shock (especially if associated with chronic occlusive disease) Phlegmasia cerulea dolens Acute compressive neuropathy Differential diagnosis for acute limb ischemia (other than acute PAD): Arterial trauma Aortic/arterial dissection Arteritis with thrombosis (e.g. giant cell arteritis, thromboangiitis obliterans) HIV arteriopathy Spontaneous thrombosis associated with a hypercoagulable state Popliteal adventitial cyst with thrombosis Popliteal entrapment with thrombosis Compartment syndrome Acute PAD: Thrombosis of an atherosclerotic stenosed artery Thrombosis of an arterial bypass graft Embolism from heart, aneurysm, plaque or critical stenosis upstream (including cholesterol or atherothrombotic emboli secondary to endovascular procedures) Thrombosed aneurysm with or without embolization

Electrocardiogram Standard chemistry Complete blood count Prothrombin time Partial thromboplastin time Creatinine phosphokinase level Patients with a suspected hypercoagulable state will need additional studies seeking: Anticardiolipin antibodies Elevated homocysteine concentration Antibodies to platelet factor IV

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Arteriography is of major value in visualizing the distal arterial tree and distinguishing patients who will benet more from percutaneous treatment than from embolectomy or open surgical procedures. Other imaging techniques that may be used to examine patients with ALI include: Computed tomographic angiography (CTA) Magnetic resonance (MR) angiography Ideally all patients with ALI should be investigated with imaging; however, the clinical condition and access to appropriate medical resources may prevent this

Figure 3. Algorithm for management of ALI1

History and physical exam Anticoagulation Doppler Category I Imaging Revascularization Category IIA Imaging Revascularization Revascularization* Amputation Category IIB Category III

Category I viable; Category IIa marginally threatened; Category IIb immediately threatened; Category III irreversible. Confirming absent or severely diminished ankle pressure/signals. *In some centers imaging would be performed

Surgical interventions and endovascular procedures are used to treat patients with ALI. The results of randomized clinical trials demonstrate that both procedures are equally efcacious.4

Treatment of acute limb ischemia

Endovascular procedures for acute
The initial goal of treatment for ALI is to prevent thrombus propagation and worsening ischemia. This can be achieved through immediate anticoagulation with heparin. Intravenously administered unfractionated heparin should be used as the standard therapy, unless the patient has antibodies against heparin (Figure 3) 14 15

limb ischemia Pharmacologic thrombolysis

Catheter-directed thrombolytic (CDT) therapy is the initial treatment of choice for patients in whom the degree of severity allows time (i.e. Categories I and IIa).

The choice of lytic therapy depends on several factors including: Location and anatomy of lesions Duration of symptoms Patient risk factors (co-morbidities) Procedural risk

If the limb is not immediately or irreversibly threatened, CDT offers a lower-risk opportunity for arterial revascularization Using CDT, the underlying lesions can be further dened by angiography When thrombolysis reveals underlying localized arterial disease, catheter-based revascularization may be more suitable.

The data from the randomized, prospective studies in ALI, suggest that CDT may offer advantages when compared with surgical revascularization. These advantages include: Reduced mortality rates Less complex surgical procedure in exchange for a higher rate of failure to avoid persistent or recurrent ischemia, major complications and ultimate risk of amputation The advantages of CDT: Reperfusion with CDT is achieved at a lower pressure and may reduce the risk of reperfusion 16 injury compared with open surgery In practice, a combination of PAT/PMT and pharmacologic thrombolytic agents is almost always used 17 Combination of PAT/PMT with pharmacologic thrombolysis may substantially speed up clot lysis in advanced ALI where time to revascularization is critical. Alternative non-surgical modalities for the treatment of ALI without the use of pharmacologic thrombolytic agents include: Percutaneous aspiration thrombectomy (PAT) Percutaneous mechanical thrombectomy (PMT)

Surgery
Surgery may be considered in trauma, where there are contraindications to CDT, or where CDT is not available. The method of revascularization (open surgical or endovascular) may differ depending on: Anatomic location of occlusion Etiology of ALI Contraindications to open or endovascular treatment Local practice patterns

Immediate post-procedural issues

Reperfusion injury: compartment syndrome
Extremity reperfusion leads to increased vascular permeability, resulting in local edema and compartment hypertension. This condition causes: Regional venule obstruction Nerve dysfunction Capillary and arteriolar obstruction Muscle pain and nerve infarction

Amputation
Up to 30% of patients with ALI require amputation.2 The amputation procedure is usually complicated by: Bleeding (due to an increased prevalence of concomitant anticoagulation) Calf muscle deterioration (which dictates that most of the amputations are above the knee) 1015% of patients limbs thought to be salvageable ultimately require major amputation, and 10% 18 of patients with ALI present as unsalvageable 19 Clinical symptoms of compartment hypertension include disproportional pain, paresthesia and edema The most commonly involved compartment is the anterior compartment, but the greatest extent of functional devastation is observed when the deep posterior compartment becomes affected. Fasciotomy is clearly indicated for the treatment of this condition where the compartment pressure is 20 mmHg.

The prevalence of fasciotomy treatment: In the United States, 5% of patients who have undergone successful revascularization therapy for ALI require fasciotomy 25% of patients in tertiary referral hospitals require fasciotomy treatment, for presumably more severe cases of ALI7 Myoglobinuria occurs in up to 20% of patients following revascularization Half of patients with creatine kinase levels >5000 units/L will develop acute renal failure Urine myoglobin >1142 nmol/L (>20 mg/dL) is also predictive of acute renal failure

Clinical outcomes
Systemic/limb
Mortality rates for ALI range from 1520%. Major morbidities include: Due to major bleeding 1015% of patients require transfusion/and or operative intervention Amputation (2530% of patients) Fasciotomy (525% of patients) Renal insufciency (up to 20% of patients)

Follow-up care
All postoperative patients should be given warfarin, often for 36 months or longer. Patients with thromboembolism will need long-term anticoagulation, possibly lifelong. If long-term anticoagulation is contraindicated due to bleeding risk factors, platelet inhibition therapy should be considered. Many patients require lifelong anticoagulation due to the high risk of recurrent limb ischemia

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References

Key points therapeutic options

A Doppler assessment should be used to conrm diagnosis of ALI A vascular specialist should evaluate all patients with suspected ALI to determine which therapeutic approach should be used initially All patients with ALI should receive parenteral anticoagulation therapy. The standard treatment used is unfractionated heparin Fasciotomy is the recommended treatment option for patients with compartment syndrome Despite appropriate treatment, up to one in four patients suffer major amputation
1. Norgren L, Hiatt WR et al., Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). Available at: www.tasc-2-pad.org. Last accessed October 2007.* 2. Rajan DK, et al. Quality improvement guidelines for percutaneous management of acute limb ischemia. J Vasc Interv Radiol 2005; 16(5): 585595. 3. Hirsch AT, et al. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic). Circulation 2006; 113(11): e463654. 4. Berridge DC, et al. Surgery versus thrombolysis for acute limb ischaemia: initial management. Cochrane Database Syst Rev 2002; Issue 3: CD002784. 5. Campbell WB, et al. Current management of acute leg ischaemia: results of an audit by the Vascular Surgical Society of Great Britain and Ireland. Br J Surg 1998; 85(11): 14981503. 6. Rutherford RB, et al. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg 1997; 26(3): 517538. 7. Eliason JL, et al. A national and single institutional experience in the contemporary treatment of acute lower extremity ischemia. Ann Surg 2003; 238(3): 382389.

*Also published as follows: J Vasc Surg 2007; 45(Suppl S): S567. Eur J Vasc Endovasc Surg 2007; 33(Suppl 1): S175. Int Angiol 2007; 26(2): 8157.

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TASC
II
Inter-Society Consensus for the Management of PAD

This pocket guide is one of a series of booklets designed to present the TASC II guidelines in a quick reference format. You can nd pocket guides on other topics covered in the TASC II guidelines on the TASC II website: www.tasc-2-pad.org

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