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					Peripheral Vascular Disease: Introduction                         2.   Risk factors for PVD include smoking, hyperlipidemia,
Background                                                             diabetes mellitus, and hyperviscosity.
Peripheral vascular disease (PVD) is a nearly pandemic            3.   Other etiologies for developing PVD may include
condition that has the potential to cause loss of limb or even         phlebitis, injury or surgery, and autoimmune disease,
loss of life. Peripheral vascular disease manifests as                 including vasculitides, arthritis, or coagulopathy.
insufficient tissue perfusion         caused by existing              PVD rarely exhibits an acute onset; it instead manifests a
atherosclerosis that may be acutely compounded by either               more chronic progression of symptoms.
emboli or thrombi. Many people live daily with peripheral             Patients with acute emboli causing limb ischemia may
vascular disease; however, in settings such as acute limb              have new or chronic atrial fibrillation, valvular disease, or
ischemia, this pandemic disease can be life threatening and            recent MI, whereas a history of claudication, rest pain, or
can require emergency intervention to minimize morbidity               ulceration suggests thrombosis of existing PVD.
and mortality.                                                        Radiation-induced PAD is becoming more common,
Pathophysiology                                                        perhaps due to the efficacy of current antineoplastic
PVD, also known as arteriosclerosis obliterans, is primarily           treatment and increased survival.
the result of atherosclerosis. The atheroma consists of a core    4.   Intermittent claudication may be the sole manifestation
of cholesterol joined to proteins with a fibrous intravascular         of early symptomatic PVD. The level of arterial
covering. The atherosclerotic process may gradually progress           compromise and the location of the claudication are
to complete occlusion of medium and large arteries. The                closely related as follows:
disease typically is segmental, with significant variation from       Aortoiliac disease manifests as pain in the thigh and
patient to patient.                                                    buttock, whereas femoral-popliteal disease manifests as
Vascular disease may manifest acutely when thrombi,                    pain in the calf.
emboli, or acute trauma compromises perfusion.                        Symptoms are precipitated by walking a predictable
Thromboses are often of an atheromatous nature and occur               distance and are relieved by rest.
in the lower extremities more frequently than in the upper            Collateral circulation may develop, reducing the
extremities. Multiple factors predispose patients for                  symptoms of intermittent claudication, but failure to
thrombosis. These factors include sepsis, hypotension, low             control precipitant factors and risk factors often causes
cardiac output, aneurysms, aortic dissection, bypass grafts,           its reemergence.
and underlying atherosclerotic narrowing of the arterial              Claudication may also present as the hip or leg "giving
lumen.                                                                 out" after a certain period of exertion and may not
Emboli, the most common cause of sudden ischemia, usually              demonstrate the typical symptom of pain on exertion.
are of cardiac origin (80%); they also can originate from             The pain of claudication usually does not occur with
proximal atheroma, tumor, or foreign objects. Emboli tend to           sitting or standing.
lodge at artery bifurcations or in areas where vessels            5.   Ischemic rest pain is more worrisome; it refers to pain in
abruptly narrow. The femoral artery bifurcation is the most            the extremity due to a combination of PVD and
common site (43%), followed by the iliac arteries (18%), the           inadequate perfusion.
aorta (15%), and the popliteal arteries (15%).                        Ischemic rest pain often is exacerbated by poor cardiac
The site of occlusion, presence of collateral circulation, and         output.
nature of the occlusion (thrombus or embolus) determine the
                                                                      The condition is often partially or fully relieved by placing
severity of the acute manifestation. Emboli tend to carry
                                                                       the extremity in a dependent position, so that perfusion
higher morbidity because the extremity has not had time to
                                                                       is enhanced by the effects of gravity.
develop collateral circulation. Whether caused by embolus or
                                                                  6.   Leriche syndrome is a clinical syndrome described by
thrombus, occlusion results in both proximal and distal
                                                                       intermittent claudication, impotence, and significantly
thrombus formation due to flow stagnation.
                                                                       decreased or absent femoral pulses. This syndrome
                                                                       indicates chronic peripheral arterial insufficiency due to
History                                                                narrowing of the distal aorta.
The primary factor for developing peripheral vascular disease     7.   The patient's medications may provide a clue to the
(PVD) is atherosclerosis.                                              existence of PVD.
1. Other maladies that often coexist with PVD are coronary            Pentoxifylline is a commonly used medication specifically
    artery disease (CAD), myocardial infarction (MI), atrial           prescribed for PVD.
    fibrillation, transient ischemic attack, stroke, and renal        Daily aspirin commonly is used for prevention of cardiac
    disease. Studies have suggested that even asymptomatic             disease (CAD), but PVD often coexists, to some degree,
    peripheral arterial disease (PAD) is associated with               in patients with CAD.
    increased CAD mortality.
Physical                                                               Deep             Venous Trauma,        Peripheral     Vascular
A systematic examination of the peripheral vasculature is              Thrombosis          and Injuries
critical for proper evaluation.                                        Thrombophlebitis
1. Peripheral signs of peripheral vascular disease are the             Workup
      classic "5 P's":
                                                                       Laboratory Studies
            o Pulselessness
                                                                       1. Routine blood tests generally are indicated in the
            o Paralysis
                                                                           evaluation of patients with suspected serious
            o Paraesthesia
                                                                           compromise of vascular flow to an extremity. CBC, BUN,
            o Pain
                                                                           creatinine, and electrolytes studies help evaluate factors
            o Pallor
                                                                           that might lead to worsening of peripheral perfusion.
2. Paralysis and paraesthesia suggest limb-threatening
                                                                           Risk factors for the development of vascular disease
      ischemia and mandate prompt evaluation and
                                                                           (lipid profile, coagulation tests) can also be evaluated,
                                                                           although not necessarily in the ED setting.
3. Assess the heart for murmurs or other abnormalities.
                                                                       2. An ECG may be obtained to look for evidence of
      Investigate all peripheral vessels, including carotid,
                                                                           dysrhythmia, chamber enlargement, or MI.
      abdominal, and femoral, for pulse quality and bruit. Note
                                                                       3. Elevated levels of inflammatory blood markers such as D
      that the dorsalis pedis artery is absent in 5-8% of normal
                                                                           dimer, C-reactive protein, interleukin 6, and
      subjects, but the posterior tibial artery usually is present.
                                                                           homocysteine have been linked to decreased lower
      Both pulses are absent in only about 0.5% of patients.
                                                                           extremity tolerance of exercise. Higher levels of activity
      Exercise may cause the obliteration of these pulses.
                                                                           in daily life have been shown to decrease these
4. The Allen test may provide information on the radial and
                                                                           levels. The applicability to practice in Emergency
      ulnar arteries.
                                                                           Medicine is unknown.
5. The skin may have an atrophic, shiny appearance and
                                                                       Imaging Studies
      may demonstrate trophic changes, including alopecia;
                                                                       1. Plain films are of little use in the setting of PVD. Doppler
      dry, scaly, or erythematous skin; chronic pigmentation
                                                                           ultrasonographic studies are useful as primary
      changes; and brittle nails.
                                                                           noninvasive studies to determine flow status. Upper
6. Advanced PVD may manifest as mottling in a "fishnet
                                                                           extremities are evaluated over the axillary, brachial,
      pattern" (livedo reticularis), pulselessness, numbness, or
                                                                           ulnar, and radial arteries. Lower extremities are
      cyanosis. Paralysis may follow, and the extremity may
                                                                           evaluated over the femoral, popliteal, dorsalis pedis, and
      become cold; gangrene eventually may be seen. Poorly
                                                                           posterior tibial arteries. Note the presence of Doppler
      healing injuries or ulcers in the extremities help provide
                                                                           signal and the quality of the signal (ie, monophasic,
      evidence of preexisting PVD.
                                                                           biphasic, triphasic). The presence of distal flow does not
7. The ankle-brachial index (ABI) can be measured at
                                                                           exclude emboli or thrombi because collateral circulation
      bedside. Using Doppler ultrasonography, the pressure at
                                                                           may provide these findings.
      the brachial artery and at the posterior tibialis artery is
                                                                       2. Magnetic resonance imaging (MRI) may be of some
      measured. The ankle systolic pressure is divided by the
                                                                           clinical benefit due to its high visual detail. Plaques are
      brachial pressure, both measured in the supine position.
                                                                           imaged easily, as is the difference between vessel wall
      Normally, the ratio is more than 1. In severe disease, it is
                                                                           and flowing blood. MRI also has the benefits of
      less than 0.5.
                                                                           angiography to provide even higher detail and can
8. A semiquantitative assessment of the degree of pallor
                                                                           replace traditional arteriography. The utility of MRI is
      also may be helpful. While supine, the degree of pallor is
                                                                           limited in the emergency setting, often due to location of
                                                                           the device and the technical skill required to interpret
 If pallor manifests when the extremity is level, the pallor
                                                                           the highly detailed images.
      is classified as level 4.
                                                                       3. Computerized tomography (CT) can be of use to the
 If not, the extremity is raised 60°. If pallor occurs within
                                                                           emergency physician since it does not have the time and
      30 seconds, it is a level 3; in less than 60 seconds, level 2;
                                                                           availability constraints of MRI. Although noncontrast
      in 60 seconds, level 1; and no pallor within 60 seconds,
                                                                           studies can be useful to image calcification and
      level 0.
                                                                           arteriosclerosis, contrast studies are most useful to
Differential Diagnoses
                                                                           image arterial insufficiency. Renal function should be
Aneurysm, Abdominal          Lumbar    (Intervertebral)        Disk        confirmed before contrast administration, since PVD
                             Disorders                                     often coexists with risk factors for contrast-induced renal
Ankle Injury, Soft Tissue    Thrombophlebitis, Septic                      failure.
Back Pain, Mechanical        Thrombophlebitis, Superficial
Other Tests                                                          in both dosage and time of administration. Remember that
1. The ankle-brachial index (ABI) is a useful test to compare        intra-arterial thrombolysis remains investigational. Obviously,
     pressures in the lower extremity to the upper extremity.        such thrombolytic therapy is contraindicated in the presence
     Blood pressure normally is slightly higher in the lower         of active internal bleeding, intracranial bleeding, or bleeding
     extremities than in the upper extremities. Comparison to        at noncompressible sites.
     the contralateral side may suggest the degree of                Consultations
     ischemia.                                                       Early surgical consultation in patients with acute limb
2. The ABI is obtained by applying blood pressure cuffs to           ischemia is prudent. Depending on the case, the surgeon may
     the calf and the upper arm. The blood pressure is               involve interventional radiology or proceed operatively.
     measured, and the systolic ankle pressure is divided by         Emboli may be treated successfully by Fogarty catheter (ie,
     the systolic brachial pressure. Normal ABI is more than 1;      an intravascular catheter with a balloon at the tip). The
     a value less than 0.95 is considered abnormal. This test        balloon is passed distal to the lesion; the balloon is inflated,
     can be influenced by arteriosclerosis and small vessel          and the catheter is withdrawn along with the embolus. This
     disease (eg, diabetes), reducing reliability. Progressive       technique most commonly is used for iliac, femoral, or
     PAD, indicated by ABI decline of greater than 0.15, has         popliteal emboli.
     been associated with increased cardiovascular disease           Definitive treatment of hemodynamically significant
     risk.                                                           aortoiliac disease is usually by aortobifemoral bypass. Its 5-
3. Transcutaneous oximetry affords assessment of impaired            year patency rate is approximately 90%. Those patients in
     flow secondary to both microvascular and macrovascular          whom PVD becomes significant, however, often have a
     disruption. Its use is increasing, especially in the realm of   plethora of comorbid medical conditions, such as
     wound care and patients with diabetes. Transcutaneous           cardiovascular disease, diabetes, and chronic obstructive
     oximetry has not been studied extensively in emergent           pulmonary disease, which increase procedural morbidity and
     occlusion.                                                      mortality. Axillobifemoral bypass and femoral-femoral bypass
Procedures                                                           are alternatives, both of which have lower 5-year patencies
The criterion standard for intraluminal obstruction has              but have lower procedural mortality.
always been arteriography, although this is both potentially         Some areas of arteriostenosis can be revascularized with
risky and often unobtainable in the emergency setting. The           percutaneous transluminal coronary angioplasty (PTCA). If
delay associated with obtaining arteriography in the setting         the occlusion is complete, a laser may be useful in making a
of obvious limb ischemia can delay definitive treatment to           small hole through which to pass the balloon. Restenosis is a
deleterious effect. If time allows, arteriography can prove          concern with PTCA, particularly for larger lesions. Stents and
useful in discriminating thrombotic disease from embolic             lasers are still considered experimental.
disease.                                                             An initial study shows promise in relieving the pain of PAD
Treatment                                                            with topically applied lidocaine spray. Suzuki and colleagues
Prehospital Care                                                     studied 24 subjects with PAD and noted a significant drop in
Prehospital care for peripheral vascular disease (PVD)               pain associated with PAD by applying an 8% lidocaine
involves the basics: control ABCs, obtain intravenous access,        metered dose spray to the affected areas. Blood levels of
and administer oxygen. Generally, do not elevate the                 lidocaine were minimal, and this technique may show
extremity. Note and record distal pulses and skin condition.         promise for those affected with focal PAD pain.
Perform and document a neurological examination of the               Medication
affected extremities.                                                The goal of pharmacotherapy is to reduce morbidity and to
Emergency Department Care                                            prevent complications.
Attention to the ABCs, intravenous access, and obtaining             Anticoagulants
baseline laboratory studies should occur early in the ED visit.      Anticoagulants reduce thrombin generation and fibrin
Obtain an ECG and chest radiograph.                                  formation and minimize clot propagation.
Treatment of either thrombi or emboli in the setting of              Heparin
peripheral vascular disease is similar. Empirically, initiate a      Augments activity of antithrombin III and prevents
heparin infusion with the goal of increasing activated partial       conversion of fibrinogen to fibrin. Does not actively lyse but
thromboplastin time to 1.5 times normal levels. Acute leg            is able to inhibit further thrombogenesis. Prevents
pain correlated with a cool distal extremity, diminished or          reaccumulation of clot after spontaneous fibrinolysis.
absent distal pulses, and an ankle blood pressure less than 50       Adult
mm Hg should prompt consideration of emergent surgical               80 U/kg IV bolus, followed by infusion of 18 U/kg/h
In some cases of emboli, intra-arterial thrombolytic agents
may be useful. The exact technique of administration varies,
Follow-up                                                           cannot maximally increase in muscle tissue because of
Further Outpatient Care                                             proximal arterial stenoses. When the metabolic demands of
1. Patients who have significant peripheral vascular disease        the muscle exceed blood flow, claudication symptoms ensue.
    but whose illness is not so severe or acute that it             At the same time, a longer recovery period is required for
    requires inpatient treatment may be discharged with             blood flow to return to baseline once exercise is terminated.
    appropriate follow-up. However, counsel these patients          Similar abnormal alterations occur in distal perfusion
    regarding the potential effects of various activities and       pressure in affected extremities. In normal extremities, the
    medications on the course of their illness. Advise              mean blood pressure drop from the heart to the ankles is no
    patients to stop smoking and to avoid cold exposures            more than a few millimeters of mercury. In fact, as pressure
    and medications that can lead to vasoconstriction,              travels distally, the measured systolic pressure actually
    including medications used for migraines and over-the-          increases because of the higher resistance encountered in
    counter medications.                                            smaller-diameter vessels.
2. Some recreational drugs (eg, cocaine) may have a                 At baseline, a healthy person may have a higher measured
    deleterious effect on peripheral arterial tone, and beta-       ankle pressure than arm pressure. When exercise begins, no
    blockers may exacerbate the condition.                          change in measured blood pressure occurs in the healthy
3. Consultation with providers who will be following the            extremity.
    patient after ED discharge is advised when making               In the atherosclerotic limb, each stenotic segment acts to
    decisions regarding the discontinuation of medications          reduce the pressure head experienced by distal muscle
    used for chronic medical conditions.                            groups. Correspondingly, at rest, the measured blood
                                                                    pressure at the ankle is less than that of a healthy person.
                                                                    Once physical activity starts, the reduction in pressure
                                                                    produced by the atherosclerotic lesion becomes more
Peripheral Arterial Occlusive Disease
                                                                    significant and the distal pressure is greatly diminished.
                                                                    The phenomenon of increased blood flow causing decreased
Background                                                          pressure distally to an area of stenosis is a matter of physics.
Claudication, which is defined as reproducible ischemic             Poiseuille calculated energy losses across areas of resistance
muscle pain, is one of the most common manifestations of            with varying flow rates by using the following equation, in
peripheral vascular disease caused by atherosclerosis.              which Q is flow, v is viscosity, L is the length of the stenotic
Claudication occurs during physical activity and is relieved        area, r is the radius of the open area within the stenosis, and
after a short rest. Pain develops because of inadequate blood       k is constant:
flow.                                                               Resistance = pressure = Q8vL/kr4
Pathophysiology                                                     Applying this equation, the pressure gradient is directly
Single or multiple arterial stenoses produce impaired               proportional to the flow and length of stenosis and inversely
hemodynamics at the tissue level in patients with peripheral        proportional to the fourth power of the radius.
arterial occlusive disease (PAOD), shown below. Arterial            Therefore, while increasing the rate of flow directly increases
stenoses lead to alterations in the distal pressures available      the pressure gradient at any given radius, these effects are
to affected muscle groups and to blood flow.                        much less marked than those due to changes in the radius of
                                  Peripheral arterial occlusive     the stenosis.
                                  disease. This angiogram shows
                                                                    As the radius is raised to the fourth power, it has the most
                                  a superficial femoral artery
                                                                    dramatic impact on a pressure gradient across a lesion. This
                                  occlusion on one side (with
                                  reconstitution of the
                                                                    impact is additive when 2 or more occlusive lesions are
                                  suprageniculate popliteal         located sequentially within the same artery.
                                  artery) and superficial femoral   Frequency
                                  artery stenosis on the other      United States
                                  side. This is the most common     Atherosclerosis affects up to 10% of the Western population
                                  area for peripheral vascular      older than 65 years. With the elderly population expected to
                                  disease.                          increase 22% by the year 2040, atherosclerosis is expected to
Under resting conditions, normal blood flow to extremity            have a huge financial impact on medicine. When claudication
muscle groups averages 300-400 mm/min. Once exercise                is used as an indicator, estimates are that 2% of the
begins, blood flow increases up to 10-fold owing to the             population aged 40-60 years and 6% older than 70 years are
increase in cardiac output and compensatory vasodilation at         affected.
the tissue level. When exercise ceases, blood flow returns to       Mortality/Morbidity
normal within minutes.                                              The most feared consequence is severe limb-threatening
In patients with PAOD, resting blood flow is similar to that of     ischemia leading to amputation. However, studies of large
a healthy person. However, during exercise, blood flow
patient groups with claudication reveal that amputation is         5.  The perceived significance of claudication is variable.
uncommon. Boyd prospectively followed 1440 patients with               Most patients appear to accept a decrease in walking
intermittent claudication for as long as 10 years and reported         distance as a normal part of aging. Investigators report
that only 12.2% required amputation. In the Framingham                 that 50-90% of patients with definite intermittent
study, only 1.6% of patients with claudication reached the             claudication do not report this symptom to their
amputation stage after 8.3 years of follow-up.                         clinician.
1. Limb amputation largely depends on the number and               6. Atherosclerosis is a systemic disease process. Patients
     severity of cardiovascular risk factors (ie, smoking,             who present with claudication due to PAOD can be
     hypertension, diabetes). Continued smoking has been               expected to have atherosclerosis elsewhere. A full
     identified as the most consistent adverse risk factor             assessment of the patient's risk factors for vascular
     associated with the progression of peripheral arterial            disease should be performed.
     occlusive disease (PAOD). Other factors are the severity      7. The risk factors for PAOD are the same as those for
     of disease at the time of the initial patient encounter           coronary artery disease or cerebrovascular disease and
     and, in some studies, the presence of diabetes.                   include diabetes, hypertension, hyperlipidemia, family
2. As with most patients with vascular disease, survival is            history, sedentary lifestyle, and tobacco use.
     less than that of age-matched control groups. Coronary        8. Smoking is the greatest of all the cardiovascular risk
     artery disease with a subsequent myocardial event is the          factors. The mechanism by which smoking causes or
     major contributor to outcome. Predicted mortality rates           accentuates atherosclerosis is unknown. What is known
     for patients with claudication at 5, 10, and 15 years of          is that the degree of damage is directly related to the
     follow-up are approximately 30%, 50%, and 70%,                    amount of tobacco used. Counseling patients on the
     respectively.                                                     importance of smoking cessation is paramount in PAOD
Race                                                                   management.
Peripheral arterial occlusive disease (PAOD) has no racial         Physical
predilection.                                                      Essential to the physical examination of a patient with
Sex                                                                claudication is a complete lower extremity evaluation and
1. Intermittent claudication most commonly manifests in            pulse examination, including measuring segmental pressures,
     men older than 50 years.                                      as depicted in the image below. Atrophy of calf muscles, loss
2. Although younger patients may present with symptoms             of extremity hair, and thickened toenails are clues to
     consistent with intermittent claudication, other              underlying peripheral arterial occlusive disease (PAOD).
     etiologies of leg pain and claudication (eg, popliteal                                                 Peripheral arterial
     entrapment syndrome) must be strongly considered.                                                      occlusive    disease.
Clinical                                                                                                    Measuring
History                                                                                                     segmental pressures.
Intermittent claudication typically causes pain that occurs
with physical activity. Determining how much physical
activity is needed before the onset of pain is crucial.
1. Typically, vascular surgeons relate the onset of pain to a
     particular walking distance in terms of street blocks (eg,
     2-block claudication). This helps to quantify patients with   1.   Palpation of pulses should be attempted from the
     some standard measure of walking distance before and               abdominal aorta to the foot, with auscultation for bruits
     after therapy.                                                     in the abdominal and pelvic regions. This can be difficult
2. Other important aspects of claudication pain are that the            in a patient who is obese, in whom palpable pulses may
     pain is reproducible within the same muscle groups and             be hidden under a deep subcutaneous layer.
     that it ceases with a resting period of 2-5 minutes.          2.   Except in the rare case of a congenital absence of a pulse
3. Location of the pain is determined by the anatomical                 (eg, persistent sciatic artery), the absence of a pulse
     location of the arterial lesions. Peripheral arterial              signifies arterial obstruction proximal to the area
     occlusive disease (PAOD) is most common with the distal            palpated. For example, if no femoral artery pulse is
     superficial femoral artery (located just above the knee            palpated, significant PAOD is present in the aortoiliac
     joint), which corresponds to claudication in the calf              distribution. The same can be said if no palpable
     muscle area (the muscle group just distal to the arterial          popliteal artery pulse is present because of existing
     disease).                                                          superficial femoral artery occlusive disease.
4. When atherosclerosis is distributed throughout the              3.   Patients who report intermittent claudication and have
     aortoiliac area, thigh and buttock muscle claudication             palpable pulses can present a clinical dilemma.
  If the history is consistent with typical claudication        3. Neurospinal disease: Pain occurs in the morning and is
   symptoms, the clinician can have the patient walk                not relieved by short resting periods. Neurospinal pain is
   around the office (or perform toe raises) until the              frequently relieved by leaning forward against a solid
   symptoms are reproduced and then palpate for pulses.             surface or by sitting.
 The exercise should cause the atherosclerotic lesion to        4. Chronic compartment syndrome: This is rare. It is usually
   become significant and should diminish the strength of           observed in runners and other athletes with large,
   the pulses distal to the lesion.                                 developed calf muscles. Muscles swell during activity,
4. When palpable pulses are not present, further                    leading to increased compartment pressure and
   assessment of the circulation can be made with a                 decreased venous return. Consistent with claudication
   handheld Doppler device.                                         pain, this pain occurs with exercise and is relieved with
 An audible Doppler signal assures the clinician that some         rest. However, the type of exercise is at a more
   blood flow is perfusing the extremity.                           strenuous level and the recovery period is prolonged.
 If no Doppler signals can be heard, a vascular surgeon         5. Popliteal entrapment syndrome: This syndrome is similar
   should be immediately consulted.                                 to intermittent claudication but is usually observed in
5. Pressure measurements can be performed to gain                   active young people. The syndrome is caused by various
   objective data on the circulatory status.                        abnormal anatomical configurations of the insertion of
 To obtain an accurate pressure reading, (1) place the             the medial gastrocnemius muscle head, which causes
   pneumatic cuff around the ankle, (2) position the                compression of the popliteal artery. Upon physical
   Doppler probe over the dorsalis pedis or posterior tibial        examination, tibial pulses may disappear when the knee
   artery, and (3) inflate the cuff to a reading above the          is at full extension. Pain is aggravated with walking but
   systolic pressure and deflate. The systolic tone at the          not with running because knee extension is not as severe
   ankle vessel is the pressure recorded.                           with running.
 A healthy person has no pressure drop from the heart to        6. Reflex sympathetic dystrophy or minor causalgia: This is
   the ankle. In fact, the pressure at the ankle may be 10-20       characteristically described as a burning pain. The
   mm Hg higher due to the augmentation of the pressure             superficial pain is often distributed along a somatic nerve
   wave with travel distally.                                       and is often related to a past trauma in the extremity.
 In patients with claudication, the measured pressure is        7. Diabetic neuropathy: Pain is due to a peripheral neuritis.
   diminished to some extent, depending on the severity of          Differentiation from intermittent claudication can be
   PAOD.                                                            difficult because of accompanying skin discoloration and
6. A useful tool in assessing a patient with claudication is        diminished pulses. An extensive neurologic evaluation is
   the ankle-brachial index (ABI), which is calculated as the       essential.
   ratio of systolic blood pressure at the ankle to the arm.     8. Venous thrombosis: Swelling and leg pain occur with
 Determining the ABI provides an assessment of the                 walking. Pain is relieved by extremity elevation, which
   impact that the PAOD is having on the patient. A normal          distinguishes this entity from arterial insufficiency.
   ABI is 0.9-1.1. However, any patient with an ABI less than    Workup
   0.9, by definition, has some degree of PAOD. The ABI          Laboratory Studies
   decreases with worsening PAOD.                                A laboratory workup is only helpful for identifying
 One area of inaccuracy with the ABI is in patients with        accompanying silent alterations in renal function and
   diabetes who have PAOD. Peripheral vessels in patients        elevated lipid profiles.
   with diabetes may have extensive medial layer calcinosis,     Imaging Studies
   rendering the vessel resistant to compression by the          1. Angiography still remains the criterion standard arterial
   pneumatic cuff. These patients should be referred to a            imaging study used in the diagnosis of PAOD, as depicted
   vascular laboratory for further evaluation.                       in the image below. However, this test is usually
Other Problems to Be Considered                                      reserved for when an intervention (either endovascular
Some disease processes mimic claudication symptoms and               or traditional open surgery) is planned.
must be excluded. They include the following:                    2. Monaco et al examined the effects of systematic
1. Osteoarthritis: This is associated with arthritic pain that       (routine) coronary angiography, as shown below, on
   is variable from day to day and may be aggravated by              patients undergoing surgical treatment of peripheral
   certain weather patterns or movements. Rest does not              arterial disease. Patients undergoing vascular surgery
   relieve pain.                                                     have a high-risk for cardiovascular complications and
2. Venous disease: Described as a dull, aching pain that             mortality. The authors found that routine coronary
   typically occurs at the end of the day or after prolonged         angiography had a positive impact compared with
   standing, venous disease is not exacerbated by exercise.          selectively determining if coronary angiography was
                                                                     needed. The routine coronary angiography improved
    survival (P=0.01) and no reports of death or                   3.  Additional medical treatment includes control of the
    cardiovascular events (P=0.003) occurred compared with             lipid profile, diabetes, and hypertension.
    those patients who were selectively chosen to have             Surgical Care
    coronary angiography prior to vascular surgery. The            Patients with limb-threatening ischemia or lifestyle-limiting
    authors recommend that multicenter trials confirm this         claudication are referred to a vascular surgeon. Only then
    finding in a larger population.                                does evaluation warrant an arteriogram.
3. Magnetic resonance angiography (MRA) is useful for              Medication
    imaging large and small vessels. Although MRA was              Daily aspirin is recommended for overall cardiovascular care.
    initially felt to provide inadequate images, this is no        While standard dosages range from 81-325 mg/d, no
    longer the case. With improved imaging capabilities,           consensus has been reached on the most effective dose.
    MRA can be used to not only diagnose but to help plan          Pentoxifylline (Trental) shows promise. Numerous
    the type of indicated intervention.                            randomized trials have documented modest improvements
4. Computerized tomographic angiography is another                 in walking distance when compared with placebo treatment
    modality used to image arterial disease. Unfortunately,        groups. Treatment can take 2-3 months to produce
    the study still requires a large amount of contrast media      noticeable results.
    and requires an upgraded CT scanner to reconstruct             The use of clopidogrel bisulfate (Plavix) and enoxaparin
    helpful images.                                                sodium (Lovenox) in the treatment of this entity is increasing;
5. Duplex ultrasonography is a method of evaluating the            however, further research is needed to establish clinical
    status of a patient’s vascular disease. Duplex scanning        efficacy.
    has the advantage of being noninvasive and requiring no        Cilostazol (Pletal) has recently shown increasing promise in
    contrast media. Unfortunately, duplex scanning is very         the treatment of intermittent claudication. Several
    technician dependent.                                          randomized studies have shown benefits in increasing
Treatment                                                          walking distances for both the distance before the onset of
Medical Care                                                       claudication pain and the distance before exercise-limiting
Treatment of claudication is medical, with surgery reserved        symptoms become intolerable (ie, maximal walking distance).
for severe cases.                                                  In a randomized, double-blind, placebo-controlled trial,
1. The goal of medical management is to impede the                 O’Donnell et al assessed the vascular and biochemical effects
     progression of peripheral arterial occlusive disease          of cilostazol therapy in individuals (n=80) with peripheral
     (PAOD).                                                       arterial disease. Arterial compliance, transcutaneous
 In patients who smoke, the most expedient way to                 oxygenation, ankle-brachial index, and treadmill walking
     impede the progress of PAOD is to stop tobacco use.           distance were measured. The cilostazol group had significant
 Extensive evidence indicates that smoking cessation              reduction in the augmentation index and also showed
     improves the prognosis.                                       reduction in transcutaneous oxygenation levels compared
 Improved walking distance and ankle pressure have been           with the placebo group. Mean percentage change in walking
     attributed to smoking cessation.                              distance improved more in the cilostazol group from baseline
2. Exercise plays a vital role in the treatment of                 compared with the placebo group. Lipid profiles were also
     claudication.                                                 improved in the cilostazol group. The results showed that
 Patients reduce their daily walking because of                   cilostazol is an efficacious treatment of peripheral arterial
     claudication pain and fear of further damage. This leads      disease. In addition to improving patients’ symptoms and
     to an increasingly sedentary lifestyle that is even more      quality of life, cilostazol also appeared to have beneficial
     detrimental.                                                  effects on arterial compliance.
 Regular walking programs result in substantial                   In 2009, Momsen et al evaluated the efficacy of drug therapy
     improvement in most patients with claudication.               in    improving      walking      distance  in    intermittent
     Improvements have ranged from 80-234% in controlled           claudication. Their study determined that statins seemed to
     studies.                                                      be the best in improving maximal walking distance.
 A daily walking program of 45-60 minutes is                      Cholesterol-lowering statin agents are beneficial in the
     recommended. The patient is instructed to walk until          medical therapy for peripheral arterial disease. In addition to
     claudication pain occurs, rest until the pain subsides, and   effectively lowering blood cholesterol profiles, recent
     repeat the cycle.                                             evidence from the Heart Protection Study showed that
 While the exact mechanism for improvement in walking             cholesterol-lowering statin agents (simvastatin) reduced the
     distance with exercise remains unknown, regular               rate of first major vascular events (myocardial infarction,
     exercise is thought to condition muscles to work more         stroke, or limb revascularization), with the largest benefits
     efficiently (more extraction of blood) and increase           seen in patients with peripheral vascular disease.
     collateral vessel formation.
The benefits were demonstrated regardless of the baseline          or other cerebrovascular disease). Competitively inhibits
cholesterol profile. As such, cholesterol-lowering statin          HMG-CoA, which catalyzes the rate-limiting step in
agents should be considered for medical treatment in               cholesterol synthesis. Patients should be placed on a
patients with peripheral arterial disease.                         cholesterol-lowering diet; the diet should be continued
Antiplatelet Agents                                                indefinitely.
Decrease overall risk of cardiovascular disease from               Adult
myocardial infarction and stroke. Also improve walking             40 mg PO hs if renal insufficiency not severe
distance by enhancing circulation.                                 5 mg PO hs in patients with severe renal insufficiency; not to
Aspirin (Anacin, Ascriptin, Bayer aspirin)                         exceed 10 mg/d when coadministered with fibrates (eg,
Inhibits prostaglandin synthesis, which prevents formation of      gemfibrozil), niacin (>1 g/d), or cyclosporine; not to exceed
platelet-aggregating thromboxane A2.                               20 mg/d when coadministered with verapamil or amiodarone
Adult                                                              Follow-up
81-325 mg PO qd                                                    Further Outpatient Care
Clopidogrel (Plavix)                                               1. Patients should be seen every 4-6 months to assess the
Selectively inhibits ADP binding to platelet receptor and              effects of medical therapy. Review changes in walking
subsequent ADP-mediated activation of glycoprotein                     distance, smoking habits, eating habits, and exercise
GPIIb/IIIa complex, thereby inhibiting platelet aggregation.           performance.
Indicated for reduction of atherosclerotic events.                 2. Control hypertension and diabetes if necessary. A repeat
Adult                                                                  pulse examination and ABI complete the follow-up
75 mg PO qd                                                            evaluation.
                                                                   3. Patients with worsening symptoms may require
Cilostazol (Pletal)
                                                                       intervention and referral to a vascular surgeon.
Mechanism of effects on symptoms of intermittent
claudication not fully understood. Cilostazol and several of its
                                                                   1. The most feared consequence is severe limb-threatening
metabolites      are     PDE    III    inhibitors,   inhibiting
                                                                       ischemia leading to amputation. However, studies of
phosphodiesterase activity and suppressing cAMP
                                                                       large patient groups with claudication reveal that
degradation, with a resultant increase in cAMP in platelets
                                                                       amputation is uncommon.
and blood vessels, leading to inhibition of platelet
                                                                    Boyd prospectively followed 1440 patients with
aggregation and vasodilation, respectively. Reversibly inhibits
                                                                       intermittent claudication for as long as 10 years and
platelet aggregation induced by various stimuli, including
                                                                       reported that only 12.2% required amputation.
thrombin, ADP, collagen, arachidonic acid, epinephrine, and
                                                                    In the Framingham study, only 1.6% of patients with
shear stress.
                                                                       claudication reached the amputation stage after 8.3
                                                                       years of follow-up.
100 mg PO bid at least 30 min before or 2 h after breakfast
and dinner; consider 50 mg bid if coadministered with
                                                                   1. Whether a patient progresses to limb amputation largely
inhibitors of CYP3A4 (eg, ketoconazole, itraconazole,
                                                                       depends on the number and severity of cardiovascular
erythromycin, diltiazem) or with inhibitors of CYP2C19 (eg,
                                                                       risk factors (ie, smoking, hypertension, diabetes).
                                                                   2. Continued smoking has been identified as the most
Pentoxifylline (Trental)
                                                                       consistent adverse risk factor associated with the
Indicated for treatment of patients with intermittent
                                                                       progression of the disease.
claudication due to atherosclerosis or other obstructive
                                                                   3. Other factors are the severity of disease at the time of
arteriopathies. Improves blood flow by increasing red blood
                                                                       the initial patient encounter and, in some studies, the
cell deformability, which decreases viscosity of blood.
                                                                       presence of diabetes.
                                                                   4. As with most patients with vascular disease, survival is
400 mg PO tid
                                                                       less than that of age-matched control groups. Coronary
Antilipemic Agents
                                                                       artery disease, with a subsequent myocardial event, is
These agents are beneficial in lowering blood cholesterol
                                                                       the major contributor to outcome.
profiles, which may reduce the rate of first major vascular
                                                                   5. Predicted mortality rates for patients with claudication
                                                                       at 5, 10, and 15 years of follow-up are approximately
Simvastatin (Zocor)                                                    30%, 50%, and 70%, respectively.
Reduces cardiovascular heart disease mortality and morbidity
(nonfatal myocardial infarction or stroke, revascularization
procedures) in high-risk patients (ie, existing coronary heart
disease, diabetes, peripheral vessel disease, history of stroke

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