Peripheral vascular disease (PVD) is a nearly pandemic condition that has the potential to cause loss of limb or even loss of life. PVD manifests as insufficient tissue perfusion initiated by existing atherosclerosis acutely compounded by either emboli or thrombi. Many people live daily with significant degrees of PVD; however, in settings such as acute limb ischemia, this latent disease can suddenly become life-threatening and necessitate emergency intervention to minimize morbidity and mortality.[1, 2]
For patient education information, see Peripheral Vascular Disease.
PVD, also known as arteriosclerosis obliterans, is primarily the result of atherosclerosis. The atheroma consists of a core of cholesterol joined to proteins with a fibrous intravascular covering. The atherosclerotic process may gradually progress to complete occlusion of medium-sized and large arteries. The disease typically is segmental, with significant variation from patient to patient.
Vascular disease may manifest acutely when thrombi, emboli, or acute trauma compromises perfusion. Thromboses are often of an atheromatous nature and occur in the lower extremities more frequently than in the upper extremities. Multiple factors predispose patients to thrombosis. These factors include sepsis, hypotension, low cardiac output (see the Cardiac Output calculator), aneurysms, aortic dissection, bypass grafts, and underlying atherosclerotic narrowing of the arterial lumen.
Emboli, the most common cause of sudden ischemia, usually are of cardiac origin (80%); they also can originate from proximal atheroma, tumor, or foreign objects. Emboli tend to lodge at artery bifurcations or in areas where vessels abruptly narrow. The femoral artery bifurcation is the most common site (43%), followed by the iliac arteries (18%), the aorta (15%), and the popliteal arteries (15%).
The site of occlusion, the presence of collateral circulation, and the nature of the occlusion (thrombus or embolus) determine the severity of the acute manifestation. Emboli tend to carry higher morbidity because the extremity has not had time to develop collateral circulation. Whether caused by embolus or thrombus, occlusion results in both proximal and distal thrombus formation as a consequence of flow stagnation.
Female sex appears to have an effect on outcomes after lower-extremity interventions for peripheral arterial disease (PAD). In a retrospective study (2004-2009) evaluating data from 12,379 patients (41% women) in 16 centers participating in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium PVI registry who underwent these procedures, female sex was associated with a higher rate of vascular complications, transfusions, and embolism, but no differences wer eseen for inpatient mortality, myocardial infarction (MI), or stroke or transient ischemic attack.[3] Despite the higher complication rates in women, the investigators reported similar overall procedural success rates between the sexes.
In another retrospective study that evaluated data over 6 years from 23,870 index transfemoral vascular access procedures from cross-matching the Eastern Danish Heart Registry with the Danish Vascular Registry, Dencker et al noted a low risk of major vascular complications (0.54%) with femoral access following coronary angiography and percutaneous coronary intervention (PCI).[4] Risk factors for such complications included left-side access, the presence of PAD, and female sex.[4]
The primary factor for developing peripheral vascular disease (PVD) is atherosclerosis.
Other conditions that often coexist with PVD are coronary artery disease (CAD), atrial fibrillation, cerebrovascular disease, and renal disease. PVD that coexists with CAD may indicate an increased burden of atheroma.[5] Studies have suggested that even asymptomatic peripheral arterial disease (PAD) is associated with increased CAD mortality.[6] Noninvasive tests for vascular disease—pulse wave velocity and ankle-brachial index (ABI)—have been linked with the number of vessels obstructed with CAD.[7]
Risk factors for PVD include smoking, hyperlipidemia, diabetes mellitus, and hyperviscosity.
Other etiologies for developing PVD may include phlebitis, injury or surgery, and autoimmune disease, including vasculitides, arthritis, or coagulopathy. PVD rarely exhibits an acute onset; it instead manifests a more chronic progression of symptoms. Patients with acute emboli causing limb ischemia may have new or chronic atrial fibrillation, valvular disease, or recent myocardial infarction (MI), whereas a history of claudication, rest pain, or ulceration suggests thrombosis of existing PVD. Radiation-induced PAD is becoming more common, perhaps because of the efficacy of current antineoplastic treatment and increased survival.[8]
Intermittent claudication may be the sole manifestation of early symptomatic PVD. The level of arterial compromise and the location of the claudication are closely related, as follows:
Ischemic rest pain is more worrisome; it refers to pain in the extremity that is due to a combination of PVD and inadequate perfusion. Ischemic rest pain often is exacerbated by poor cardiac output. The condition is often partially or fully relieved by placing the extremity in a dependent position, so that perfusion is enhanced by the effects of gravity.
Erectile dysfunction (ED) has been linked as a potential early indicator of both CAD and PVD.[9] Whereas many factors can contribute to ED (including obesity, lifestyle, physical activity, diabetes, and psychiatric factors), the etiology of the vasculogenic cause of ED parallels the etiology of CAD and PVD.
Leriche syndrome is a clinical syndrome described by intermittent claudication, impotence, and significantly decreased or absent femoral pulses. This syndrome indicates chronic peripheral arterial insufficiency due to narrowing of the distal aorta.
The patient's medications may provide a clue to the existence of PVD. Pentoxifylline is a commonly used medication specifically prescribed for PVD. Daily aspirin commonly is used for prevention of cardiac disease (CAD), but PVD often coexists, to some degree, in patients with CAD.
A systematic examination of the peripheral vasculature is critical for proper evaluation.
Peripheral signs of peripheral vascular disease are the classic "five P's," as follows:
Paralysis and paresthesia suggest limb-threatening ischemia and mandate prompt evaluation and consultation.
Assess the heart for murmurs or other abnormalities. Investigate all peripheral vessels, including carotid, abdominal, and femoral, for pulse quality and bruit. Note that the dorsalis pedis artery is absent in 5-8% of normal subjects, but the posterior tibial artery usually is present. Both pulses are absent in only about 0.5% of patients. Exercise may cause the obliteration of these pulses.
The Allen test may provide information on the radial and ulnar arteries.
The skin may have an atrophic, shiny appearance and may demonstrate trophic changes, including alopecia; dry, scaly, or erythematous skin; chronic pigmentation changes; and brittle nails.
Advanced PVD may manifest as mottling in a "fishnet pattern" (livedo reticularis), pulselessness, numbness, or cyanosis. Paralysis may follow, and the extremity may become cold; gangrene eventually may be seen. Poorly healing injuries or ulcers in the extremities help provide evidence of preexisting PVD.
The ABI can be determined at the bedside. Pressure is measured with Doppler ultrasonography at the brachial artery and at the posterior tibialis artery. The ankle systolic pressure is divided by the brachial pressure, both as measured in the supine position. Normally, the ratio is greater than 1. In severe disease, it is less than 0.5.
A semiquantitative assessment of the degree of pallor also may be helpful. While the patient is supine, the degree of pallor is assessed. If pallor manifests when the extremity is level, the pallor is classified as level 4. If not, the extremity is raised 60°. If pallor occurs in 30 seconds or less, it is a level 3; if in less than 60 seconds, level 2; and if in 60 seconds, level 1. If no pallor occurs within 60 seconds, it is level 0.
Routine blood tests may be indicated in the evaluation of patients with suspected serious compromise of vascular flow to an extremity. Complete blood count (CBC), blood urea nitrogen (BUN), creatinine, and electrolyte studies help evaluate for signs of end-organ injury and for factors that might lead to worsening of peripheral perfusion. Risk factors for the development of vascular disease (lipid profile, coagulation tests) can also be evaluated, though not necessarily in the emergency department (ED) setting.
Elevated levels of inflammatory blood markers such as D dimer, C-reactive protein, interleukin-6, and homocysteine have been linked to decreased lower extremity tolerance of exercise.[10] Higher levels of activity in daily life have been shown to decrease these levels.[11] The applicability to practice in emergency medicine is not clear, but it is unlikely to be of clinical significance.
Plain films are of little use in the setting of peripheral vascular disease (PVD).
The criterion standard for intraluminal obstruction has always been arteriography, though it is both potentially risky and often unobtainable in the emergency setting. The delay associated with obtaining arteriography in the setting of obvious limb ischemia can delay definitive treatment to deleterious effect. If time allows, arteriography can prove useful in discriminating thrombotic disease from embolic disease.
Doppler ultrasonographic studies are useful as primary noninvasive studies to determine flow status. Upper extremities are evaluated over the axillary, brachial, ulnar, and radial arteries. Lower extremities are evaluated over the femoral, popliteal, dorsalis pedis, and posterior tibial arteries. Note the presence of Doppler signal and the quality of the signal (ie, monophasic, biphasic, triphasic). The presence of distal flow does not exclude emboli or thrombi because collateral circulation may provide these findings.
Magnetic resonance imaging (MRI) may be of some clinical benefit by virtue of its high visual detail. Plaques are imaged easily, as is the difference between vessel wall and flowing blood. MRI also has the benefits of angiography, providing even higher detail and capable of replacing traditional arteriography. The utility of MRI is limited in the emergency setting, often because of the location of the device and the technical skill required to interpret the highly detailed images.
Computed tomography (CT) can be of use to the emergency physician in that it does not have the time and availability constraints that MRI does. Although noncontrast studies can be useful for imaging calcification and arteriosclerosis, contrast studies are most useful for imaging arterial insufficiency. Renal function should be confirmed before contrast administration; PVD often coexists with risk factors for contrast-induced renal failure. High-definition CT studies in patients who exhibit symptoms of PVD can be of benefit in guiding treatment decisions and modalities.[12]
CT angiography (CTA) and magnetic resonance angiography (MRA) represent significant developments in axial imaging of PVD. Benefits of CTA include rapid noninvasive acquisition, wide availability, high spatial resolution, and the ability to generate isotropic datasets on 64-detector-row and higher CT scanners; drawbacks include the exposure to iodinated contrast and ionizing radiation. Benefits of MRA include high diagnostic accuracy and the avoidance of exposure to ionizing radiation; drawbacks include limited availability and increased cost.[13]
Molecular imaging with radionuclide-based approaches may potentially provide a novel noninvasive assessment of biologic processes in PVD, such as angiogenesis and atherosclerosis.[14]
The ankle-brachial index (ABI) is a useful test for comparing pressures in the lower extremity with pressures in the upper extremity. Blood pressure normally is slightly higher in the lower extremities than in the upper. Comparison to the contralateral side may suggest the degree of ischemia.
The ABI is obtained by applying blood pressure cuffs to the calf and the upper arm. The blood pressure is measured, and the systolic ankle pressure is divided by the systolic brachial pressure. Normal ABI is higher than 1; a value less than 0.95 is considered abnormal. This test can be influenced by arteriosclerosis and small-vessel disease (eg, diabetes), which reduce its reliability. Progressive peripheral arterial disease (PAD), indicated by an ABI decline of more than 0.15, has been associated with increased cardiovascular disease risk.[15]
Transcutaneous oximetry affords assessment of impaired flow secondary to both microvascular and macrovascular disruption. Its use is increasing, especially in the realm of wound care and patients with diabetes. Transcutaneous oximetry has not been studied extensively in emergent occlusion.
An electrocardiogram (ECG) may be obtained to look for evidence of dysrhythmia, prior cardiac injury, or even acute myocardial infarction.
Therapeutic recommendations include single-agent antiplatelet agents for prevention of cardiovascular events in patients wth asymptomatic and symptomatic peripheral arterial disease (PAD).[2] These medications should be used in conjunction with efforts to reduce risk factors, including smoking cessation and exercise therapy.[16]
Statins have been linked to improved prognosis in other vasculopathies, including renovascular and cardiovascular events.[17] Although lacking an immediate effect on any vascular process, statins show promise in slowing the progression of atherosclerotic disease systemically.
When conservative measures fail to improve quality of life and function, endovascular procedures are considered.[1] However, the timing and need for revascularization are related to the general primary presentations of claudication, critical limb ischemia, and acute limb ischemia, in which urgent intervention is warranted for critical limb ischemia.[1, 2]
An emerging treatment for peripheral vascular disease (PVD) is the use of growth factor (delivered as genes or proteins) and cell therapy. The delivery of growth factors or cells to the ischemic tissue can locally stimulate the regeneration of the functional vasculature network, reperfuse the ischemic tissue, and salvage the limb.[18]
A guideline on management of patients with lower-extremity PAD has been formulated by the American Heart Association and the American College of Cardiology (see Guidelines).[19]
Prehospital care for PVD involves the basics: control ABCs (airway, breathing, circulation), obtain intravenous access, and administer oxygen. In general, do not elevate the extremity. Note and record the distal pulses and skin condition. Perform and document a neurologic examination of the affected extremities.
Early emergency department care involves attention to the ABCs, intravenous access, and obtaining baseline laboratory studies. Obtain an electrocardiogram (ECG) and a chest radiograph.
Treatment of either thrombi or emboli in the setting of peripheral vascular disease is similar. Empirically, initiate a heparin infusion with the goal of increasing activated partial thromboplastin time to 1.5 times normal levels. Acute leg pain correlated with a cool distal extremity, diminished or absent distal pulses, and an ankle blood pressure less than 50 mm Hg should prompt consideration of emergent surgical referral.
In some cases of emboli, intra-arterial thrombolytic agents may be useful. The exact technique of administration varies, in both dosage and time of administration. Remember that intra-arterial thrombolysis remains investigational. Obviously, such thrombolytic therapy is contraindicated in the presence of active internal bleeding, intracranial bleeding, or bleeding at noncompressible sites.
Early surgical consultation in patients with acute limb ischemia is prudent. Depending on the case, the surgeon may involve interventional radiology or proceed operatively. Emboli may be treated successfully by Fogarty catheter (ie, an intravascular catheter with a balloon at the tip). The balloon is passed distal to the lesion; the balloon is inflated, and the catheter is withdrawn along with the embolus. This technique most commonly is used for iliac, femoral, or popliteal emboli.
Definitive treatment of hemodynamically significant aortoiliac disease usually takes the form of aortobifemoral bypass, which has a 5-year patency rate of approximately 90%. Those patients in whom PVD becomes significant, however, often have a plethora of comorbid medical conditions, such as cardiovascular disease, diabetes, and chronic obstructive pulmonary disease, which increase procedural morbidity and mortality. Axillobifemoral bypass and femorofemoral bypass are alternatives, both of which have lower 5-year patency rates but have lower procedural mortality.
Some areas of arteriostenosis can be revascularized with percutaneous transluminal coronary angioplasty (PTCA). If the occlusion is complete, a laser may be useful in making a small hole through which to pass the balloon. Restenosis is a concern with PTCA, particularly for larger lesions. Stents and lasers are still considered experimental.
An initial study showed promise in relieving the pain of PAD with topically applied lidocaine spray. Suzuki et al studied 24 subjects with PAD and noted a significant drop in pain associated with PAD by applying an 8% lidocaine metered dose spray to the affected areas. Blood levels of lidocaine were minimal, and this technique may have therapeutic potential for those affected with focal PAD pain.[20]
Patients who have significant PVD but whose illness is not so severe or acute that it requires inpatient treatment may be discharged with appropriate follow-up. However, counsel these patients regarding the potential effects of various activities and medications on the course of their illness. Advise patients to stop smoking and to avoid cold exposures and medications that can lead to vasoconstriction, including medications used for migraines and over-the-counter medications.
Some recreational drugs (eg, cocaine) may have a deleterious effect on peripheral arterial tone, and beta-blockers may exacerbate the condition.
Consultation with providers who will be following the patient after discharge from the emergency department is advised when making decisions regarding the discontinuance of medications used for chronic medical conditions.
In November 2016, the American Heart Association (AHA) and the American College of Cardiology (ACC) published the following recommendations on lower-extremity peripheral artery disease (PAD)[19] :
The goal of pharmacotherapy is to reduce morbidity and to prevent complications.
Clinical Context: Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.
Anticoagulants reduce thrombin generation and fibrin formation and minimize clot propagation.