Epidemiology and Risk Factors of Atherosclerotic Peripheral Arterial Disease

Atherosclerotic peripheral arterial disease (PAD) causes partial or complete obstruction of the arteries in the legs. It can be proximal or distal, focal or diffuse. PAD is part of a systemic disease process and is a major cause of morbidity and mortality worldwide. Physiatrists must be knowledgeable about PAD because it affects many of the patients who are commonly seen because of its correlation with other vascular disorders like stroke. PAD also fits well in the practice of physiatry because it affects physical function and quality of life.

PAD is common in the United States, affecting around 8 million Americans.²⁵ Men present to physicians more frequently. When screening is performed on asymptomatic individuals, however, women appear to be affected as commonly as men. Blacks are more affected than other races.⁴¹ Smoking is the biggest risk factor for PAD. Smokers are at higher risk for PAD, and they develop it at an earlier age than nonsmokers.⁵¹ Diabetes is also a major risk factor for PAD. The risk of PAD increases 26% for every 1% increase in hemoglobin A1c.⁵⁸ Other factors associated with PAD include hypertension, dyslipidemia, chronic renal insufficiency, elevated inflammatory biomarkers, and hyperhomocysteinemia (Box 56-2).

Clinical Presentation of Atherosclerotic Peripheral Arterial Disease

The various clinical presentations of PAD include asymptomatic, intermittent claudication (IC), critical limb ischemia (CLI), and acute limb ischemia, with the most common being asymptomatic (Box 56-3). Only around 10% of people with PAD report symptoms of IC. Around half of PAD patients report leg symptoms other than claudication. Forty percent of people with PAD report no leg symptoms at all.²⁵

Acute Limb Ischemia

Acute arterial occlusion of the lower limb can be caused by thrombosis, embolism, or dissection (Figure 56-2). This is a limb-threatening medical emergency. The incidence is around 140 new cases per million persons per year.⁴¹ Patients present with pain, poikilothermia, and pulselessness. They might also have the classic symptoms of pallor, paresthesia, and paralysis. Symptoms are usually present for only hours to days when the patient presents. If symptoms have been present for less than 2 weeks, it is considered to be acute limb ischemia. Acute limb ischemia requires emergent vascular surgery evaluation and treatment. Just as with myocardial infarction and stroke, reperfusion must occur as soon as possible to prevent irreversible tissue loss (muscle, nerve, or limb loss). Embolectomy and thrombolysis can be attempted in appropriate patients. Up to 30 percent of patients with acute limb ischemia will require amputation in the first month of presentation.⁴¹

FIGURE 56-2 Diagnostic and treatment algorithm for a patient with acute limb pain. The foremost goal is to evaluate and treat limb-threatening arterial blockage.

Critical Limb Ischemia

CLI is chronic ischemia (Figure 56-3). CLI is ischemia of the limb for more than 2 weeks causing rest pain, ischemic ulcers, and gangrene. Because so many patients with PAD are asymptomatic, it is not uncommon for the initial presentation of PAD to be CLI. The incidence is around 500 new cases per million persons per year.⁴¹

FIGURE 56-3 Diagnostic and treatment algorithm for a patient with chronic lower extremity pain. Consideration of peripheral arterial occlusive disease (PAOD) must be given if the patient’s ankle–brachial index (ABI) is less than 0.90. However, many patients have multiple etiologies of their limb pain, for example, osteoarthritis and PAOD. LE, Lower extremity; MRA, magnetic resonance angiography; MSK, musculoskeletal; Neuro, neurologic; RP, rest pain; Statin, HMG-CoA reductase inhibitor; TL, tissue loss.

CLI generally begins once the toe pressure falls to less than 30 to 50 mm Hg. Rest pain generally does not occur until the toe pressure falls below 30 mm Hg; however, higher perfusion pressures are needed to heal wounds than are needed to maintain intact skin. A patient with a toe pressure of 40 mm Hg and intact skin can be asymptomatic but then develop a nonhealing ischemic ulcer after minor trauma. Such a patient would meet the criteria for CLI despite having no history of rest pain or IC. All patients with CLI should be urgently referred for evaluation by a vascular surgeon to see whether they are a candidate for revascularization.

Evaluation of Atherosclerotic Peripheral Arterial Disease

Vascular Testing for Peripheral Arterial Disease

Ankle–Brachial Index

PAD is usually diagnosed with the ABI, which compares the brachial systolic pressure with the ankle systolic pressure (Figure 56-4). An ABI of 0.9 or less is 95% sensitive in detecting PAD compared with angiography. The ABI is inexpensive, simple, and noninvasive, making it an appealing screening test. An ABI should be obtained on all patients over the age of 70, patients aged 50 to 69 who have cardiovascular risk factors, or any patient with symptoms of PAD or an abnormal lower limb vascular exam.⁴⁰ An ABI of 1.4 or greater is due to incompressible vessel walls at the ankle and is nondiagnostic. Patients with an elevated ABI will need additional testing such as toe pressures to evaluate for the presence of PAD. Patients with a normal ABI but a high suspicion for IC should have the ABI repeated after exercise (Figure 56-5). The ABI is related to prognosis and functional ability, and ABI can be repeated to follow disease progress.

FIGURE 56-4 Measurement of the ankle–brachial index.

(From Hiatt WR: Medical treatment of peripheral arterial disease and claudication, N Engl J Med 344:1608-1621, 2001.)

FIGURE 56-5 Evaluation of patients with suspected peripheral arterial disease: which patients should undergo screening with ankle–brachial index?

(From Hiatt WR: Medical treatment of peripheral arterial disease and claudication, N Engl J Med 344:1608-1621, 2001.)

Segmental Limb Systolic Pressure Measurement

Limb pressures are taken in the thigh, calf, and ankle. Occlusive disease is noted by a significant decrease in systolic pressure from one level to the next (Figure 56-6). Just as with the ABI, incompressible vessel walls can falsely elevate pressures and render the testing inaccurate. Small or moderate lesions can also be missed because they often do not cause a large decrease in pressure.

FIGURE 56-6 An example of segmental Doppler waveforms and systolic pressures in both legs. This patient has right-sided normal pressures and waveforms. In contrast, his left leg has evidence of occlusive disease at his superficial femoral and popliteal artery, as denoted by significant pressure decrease at these levels and changes in his Doppler waveforms.

Management of Atherosclerotic Peripheral Arterial Disease

PAD is not only underdiagnosed but it also is undertreated even after being identified.³ When treating patients with PAD, the physician and patient must remember that PAD is part of a systemic vascular disorder. Peripheral, coronary, and cerebral artery diseases are all part of systemic atherosclerosis. Patients with PAD are more likely to have coronary artery disease and cerebral artery disease than patients without PAD. Physicians and patients, however, often do not recognize PAD as an important predictor of cardiovascular morbidity and mortality and do not treat it as aggressively as coronary artery disease or cerebral artery disease.

The goals of treatment are to reduce ischemic symptoms, increase walking ability, improve function, prevent and heal wounds, prevent limb loss, and reduce morbidity and mortality. This is best accomplished using a multidisciplinary approach that includes physiatrists, primary care physicians, vascular surgeons, and the patient. Management involves education, risk factor modification, pharmacotherapy, exercise, and vascular interventions (Figure 56-7).

FIGURE 56-7 Treatment of patients with proven peripheral arterial disease.

(From Hiatt WR: Medical treatment of peripheral arterial disease and claudication, N Engl J Med 344:1608-1621, 2001.)

Wounds

Just as with ischemic pain, ischemic wounds are best treated with reperfusion of the limb (Figure 56-8). Wounds can be ischemic or neuroischemic and should be kept clean and free from necrotic debris. Sharp debridement of ischemic wounds must be done with caution because it can increase the area of ischemic necrosis. This is because the surrounding tissue might not have sufficient blood supply to repair itself after the trauma of debridement. Dry gangrene can be allowed to autoamputate as long as there is no evidence of infection and there is adequate perfusion to support healing of the underlying tissue. Appropriate orthoses and off-loading devices should be used to protect the foot from pressure and shear forces. Footwear should cover the foot to protect against trauma and have enough length, breadth, and depth to prevent pressure on the wound.

FIGURE 56-8 Diagnostic and treatment algorithm for a patient with a foot (or ankle) ulcer. Consideration of underlying peripheral arterial occlusive disease is important, as is treating osteomyelitis that can prevent this condition from healing adequately. ABI, Ankle–brachial index; PAOD, peripheral arterial occlusive disease.

Dressings should be applied to keep the wound base clean and moist, but there is no good evidence supporting any one type of dressing over another (see Chapter 32). The wound should be monitored for infection and treated immediately if detected. The ischemic foot often has dependent rubor, which can be distinguished from cellulitis by reexamining the limb after a short period of elevation. Dependent rubor should fade with elevation and is not associated with induration or increased warmth. The erythema of cellulitis is often associated with induration, increased warmth, swelling, and does not fully resolve with elevation of the limb.

Patients with ischemic wounds should be evaluated for revascularization. TcPO₂ is a useful test to predict wound healing. TcPO₂ less than 30 mm Hg is associated with poor wound healing.⁴⁶ If revascularization is not an option, amputation might be necessary. The physiatrist should be involved preoperatively in determining the level of amputation. The decision should be made based on tissue viability, function, and prosthetic options. Patients who undergo amputation of a limb should receive physical and occupational therapy for transfers, mobility, activities of daily living, and education. Prosthetic limbs should be prescribed for appropriate patients. See Chapter 13, Rehabilitation of People With Lower Limb Amputation, for a more detailed discussion.

Introduction

Thromboangiitis obliterans (TAO), also called Buerger’s disease, is a nonatherosclerotic PAD affecting young male smokers. It is an inflammatory disease that affects small- and medium-sized arteries of the upper and lower distal extremities. It also affects the veins and nerves, but it is the arterial aspect that causes the most morbidity. The disease is segmental, meaning there are normal-appearing sections of the artery interspersed with diseased sections. It is characterized by inflammatory thrombus in the small- and medium-sized arteries of the arms and legs that spares the vessel wall. It is considered to be a form of vasculitis.

Men are more affected by TAO than women. The number of affected women has increased, however, and is thought to be due to the increase in the number of women smoking. Although TAO is found worldwide, it is more common in Eastern Europe, the Middle East, and the Far East. It is a common cause of PAD in Japan and India. It is not a common cause of PAD in the United States. Unlike atherosclerotic PAD, life expectancy does not appear to be shortened. The risk of amputation is very high in patients with TAO.⁵²

The cause of TAO is unknown. Although there is a clear and strong link to smoking, the exact disease-causing mechanism is still unknown. Of the patients who continue to smoke, 43% will require an amputation. Of the patients who quit smoking, only 6% will need amputation.⁴²

Clinical Presentation, Evaluation, and Diagnosis of Thromboangiitis Obliterans

Patients typically present with claudication symptoms in the upper or lower limbs. If the patient continues to smoke, the disease will progress to rest pain and ischemic ulcers. Clinically the legs are more involved than the arms. Most patients with TAO, however, will have three or four limbs involved when assessed with angiography, even if they are symptomatic in only one limb.⁴² There have been case reports of disease in the vascular beds of the heart, lung, brain, kidney, and intestinal tract.¹⁷ Although some patients report arthralgias (which can appear long before the ischemic problems and typically resolve spontaneously), there is no erosive arthritis with TAO.

The physician should do a thorough history and physical examination when evaluating a patient suspected to have TAO. A tobacco history should be taken, including smoking and smokeless tobacco use. Pulses should be checked carefully in the upper and lower limbs. When evaluating a patient with leg-only symptoms, the physician can perform an Allen test to assess for asymptomatic involvement of the upper extremities (Figure 56-9). A positive test suggests small artery disease in the upper limbs but is not specific to TAO. Evidence of small artery disease in the lower and the upper limbs places TAO high on the list of differential diagnoses.

FIGURE 56-9 The Allen test.

(From Olin JW, Lie JT: Thromboangiitis obliterans (Buerger’s disease). In Cooke JP, Frohlich ED, editors: Current management of hypertensive and vascular diseases, St Louis, 1992, Mosby–Year Book.)

No diagnostic laboratory tests exist for TAO, but testing should be performed to rule out other diagnoses. Testing for autoimmune disorders and other forms of vasculitis should be performed and are negative in patients with TAO. Erythrocyte sedimentation rate and serum C-reactive protein are normal. Patients should be screened for diabetes, hyperlipidemia, and hypercoagulable disorders, which typically are not present in patients with TAO.⁴²

An echocardiogram should be performed to rule out a cardiac source of emboli. An arteriogram of all four limbs should be obtained. The arteriogram should assess for the presence of atherosclerosis or source of emboli, both of which should not be present in TAO. Arteriogram findings in TAO include small- and medium-sized vessel involvement with corkscrew collaterals. These findings are suggestive of, but not specific to, TAO. They are also seen with other vasculitides or autoimmune disorders, which must be ruled out with laboratory investigation as previously mentioned.

No standard set of diagnostic TAO criteria has been validated, but several criteria have been proposed.^33,42,43,59 Commonly accepted criteria are a history of tobacco use, age less than 45, distal limb ischemia, and exclusion of atherosclerosis and autoimmune and hypercoagulable disorders. For diagnostic criteria purposes, patients are considered to have limb ischemia if they have claudication, rest pain, ischemic wounds, or gangrene.

A biopsy should be performed if TAO is suspected, but the clinical picture is not typical. Pathologically the acute phase of TAO shows an occlusive thrombus that is inflammatory but which spares the vessel wall. The vessel wall is not spared in other vasculitides or in atherosclerosis.⁴²

Management of Thromboangiitis Obliterans

Smoking cessation is key to disease management. It must be made clear to patients that to continue smoking means the disease will progress and the risk of amputation will be high (Figure 56-10). Almost all patients who quit smoking can avoid amputation. Patients must understand that they control the outcome of this disease by their choice to continue smoking or not. It has been reported that smokeless tobacco and nicotine replacement patches or gum can cause disease exacerbation and should therefore not be considered as safe alternatives to smoking.²⁴

FIGURE 56-10 Patient with Buerger’s disease.

(From Stone JH: Vasculitis: a collection of pearls and myths, Rheumatic Dis Clin N Am 33:691-739, 2007.)

Revascularization is not usually a successful option for patients with TAO. Because the disease is distal and segmental, there are usually no target vessels for a bypass procedure. Trials for new treatments have been small and limited in the United States. Treatment options that have been or are being investigated either in the United States or abroad include pneumatic compression devices, prostaglandins, thrombolytics, omental transfer, electrical spinal cord stimulation, and angiogenesis. Angiogenesis has been attempted via growth factors by either direct intramuscular injection of the growth factors or gene transfer. Cell therapy has also been investigated using autologous bone marrow injection or stem cell injection. Fenestration of the tibia and intramedullary wire have also been studied.⁴⁴ Although current research gives hope for the future, the mainstay of therapy continues to be smoking cessation, local wound care, and amputation when required.

Raynaud’s Phenomenon

It is estimated that between 5% and 17% of the population might have Raynaud’s phenomenon.²⁷ It is more common in young women and those with a family history of the disorder. Although it can affect both the hands and the feet, the hands are more commonly affected.

Raynaud’s phenomenon occurs when the normal vascular response becomes exaggerated. When exposed to cold, the normal physiologic response is to decrease blood flow to the extremities. By decreasing blood flow to the extremities, the body can preserve core temperature. In Raynaud’s phenomenon, this normal vasoconstriction is exaggerated and causes color changes, pain, and numbness in the fingers and sometimes the toes. It can be triggered by cold temperatures, emotional stress, vibration, or anything that activates the sympathetic nervous system.

Typically the digits become cold and have a distinct pale or white border. They can even develop cyanosis. With rewarming and reperfusion, the skin becomes red. Patients often report that their digits are painful, numb, stiff, and clumsy during and immediately after an attack. They have trouble doing fine motor activities during this time. Symptoms typically resolve with rewarming.

Raynaud’s phenomenon is diagnosed based on a history of repeated attacks associated with color changes of the digits. Primary Raynaud’s phenomenon is not associated with connective tissue diseases or other vascular diseases. Nailfold capillary examination is normal, and the antinuclear antibody is negative.

Secondary Raynaud’s phenomenon is associated with other disorders, such as connective tissue diseases such as scleroderma and lupus. Secondary Raynaud’s phenomenon has also been reported with hypothyroidism, in which case it improves with thyroid replacement therapy. It can also be associated with occlusive peripheral vascular diseases such as TAO. Unlike the primary phenomenon, secondary Raynaud’s phenomenon is harder to control and has a less benign course. It can lead to frequent uncontrollable attacks, ischemic ulcers, and amputation.

Patients should be referred to a rheumatologist if secondary Raynaud’s phenomenon is suspected or if the nailfold capillary examination is abnormal. Nailfold capillaries are examined with an ophthalmoscope or low-powered microscope. Nailfold capillaries should be thin, parallel, and numerous. Abnormal findings include dilated or distorted loops or areas without visible capillaries.

Patients with Raynaud’s phenomenon should be instructed to keep the whole body warm, avoid sudden decreases in temperature, stop smoking, avoid caffeine, avoid sympathomimetic drugs, and reduce stress. Patients should also avoid vibration from things like power tools and lawn tools if they have vibration-induced attacks. If an attack happens, the digits should be warmed with warm (not hot water) or another source of mild warmth. Some advocate the use of calcium channel blockers for recalcitrant cases.

Livedo Reticularis

Livedo reticularis has a mottled bluish reticular appearance with no distinct border. It is not blanchable. It is seen on the arms and legs and occasionally the trunk. It is more common in young women. Cold exposure can trigger it. It is usually benign with no associated disease. If it is associated with pain or ulcers or is generalized, the patient should be evaluated for a connective tissue disorder, other underlying disease, or drug-induced etiology.

A case has been reported of a patient with livedo reticularis who required an amputation. Pathologic examination of tissue samples after amputation demonstrated TAO.⁶⁴ There have also been case reports in children of livedo reticularis developing after initiation of methylphenidate or dextroamphetamine. The physiatrist needs to be aware of this possible association because these are drugs used in rehabilitation medicine.⁶³

Treatment is generally not required unless there is an underlying disease associated with the livedo reticularis, in which case the treatment would be for the underlying disease. Drug-induced cases would be treated by stopping the offending drug.

Acrocyanosis

Acrocyanosis causes the hands and feet to be bluish and cold but is not painful. It is more common in women. It is aggravated by cold exposure but is more persistent rather than episodic, like Raynaud’s phenomenon. It does not cause ischemic ulcers or trophic changes. The pulses are normal. Generally no treatment is required.

Epidemiology of Chronic Venous Insufficiency

CVI is a common but often ignored problem. Venous ulcers caused by CVI account for 80% of all lower limb ulcers.⁴⁷ The incidence of ulceration and CVI is twice as common in women, but the sequelae of the disease and severity are higher in men than in women. Predisposing factors include occupations that require prolonged standing, obesity, positive family history, multiparity, advanced age, and history of leg injury, surgery, heart failure, paralysis, and DVT. One third of patients with CVI have history of DVT.

Pathogenesis of Chronic Venous Insufficiency

The basic underlying pathophysiologic mechanism in CVI is persistent ambulatory venous hypertension in the superficial and deep venous systems in the lower limbs. To understand the pathogenesis of venous hypertension, a basic review of the lower limb venous system is necessary (Figure 56-11).

FIGURE 56-11 A, Longitudinal duplex ultrasound image of an acute popliteal deep vein thrombosis. Note the echolucent vein. This segment is noncompressible to the vascular technician and is a useful component of the diagnosis. B, Longitudinal duplex image of a chronic popliteal deep vein thrombosis. Note the echogenic area lining the vein wall and blood flow around this narrowed area. This vein is now compressible to the vascular technician but is not as compliant as a normal vein.

Normal functioning of the venous blood flow system depends on competent valves, calf muscle pump mechanism, and normal venous anatomy. The valves found in superficial, deep, and perforating veins are one-way valves. The frequency of valves in deep veins increases from proximal to distal. Deep veins in the foot and leg contain valves at about 2-cm intervals, whereas popliteal and femoral veins have only one or two valves. Only one valve is proximal to the saphenofemoral junction, and it can be absent in 37% of the cases. Incompetence in any of these valves disrupts the unidirectional flow of blood from the superficial to the deep systems and toward the heart, resulting in ambulatory venous hypertension. Incompetence in the superficial venous system is usually caused by failure of the valves at the saphenofemoral junction or saphenopopliteal junction. Incompetence in one system can lead to incompetence in another.

Valvular incompetence can be primary or secondary. Primary valve abnormalities can be due to valvular agenesis or aplasia. The most common cause of secondary valvular dysfunction is DVT. Less frequently, pelvic or abdominal masses, surgery such as vein stripping, harvesting of vein for coronary bypass surgery, pregnancy, or trauma can alter the function of the venous system. Once venous hypertension develops, it continues to worsen through a vicious cycle. Pooled blood and venous hypertension often lead to venous dilatation, which leads to greater valvular insufficiency.

Several theories exist in regard to the cutaneous changes that occur with CVI. Current evidence suggests that the increased venous hydrostatic pressure transmitted to dermal microcapillaries leads to increased capillary permeability. This allows escape of fluid, red blood cells, and macromolecules such as fibrinogen into pericapillary tissue, with formation of fibrin cuffs around dermal capillaries. The fibrin cuffs act as a barrier to oxygen diffusion, resulting in tissue hypoxia. Growth factor and cytokines released from the activated leukocytes trapped in the fibrin cuff lead to fibrosis and inflammation.⁵³ Even though initially there is increased capillary permeability, at later stages there can be capillary thrombosis with resultant tissue hypoxia.

Clinical Features of Chronic Venous Insufficiency

Symptoms of CVI are highly variable, and the severity of symptoms might not correlate with the signs or extent of visible varices. Initial complaints can be purely cosmetic in nature with a desire for treatment for unsightly varicosities. The history can often clarify the predisposing risk factors such as prolonged standing, previous DVT, trauma, and any symptoms suggestive of PAD.

The chief clinical manifestations are dilated leg veins, edema, leg pain, skin pigmentation, subcutaneous fibrosis, dermatitis, and ulceration. Edema might be mild initially, limited to the perimalleolar area, and usually resolving after bed rest. In early stages there is soft-pitting edema, which becomes nonpitting as a result of subcutaneous fibrosis at later stages.

Although not all patients with CVI experience leg pain, several distinct types of pain are described. The pain can be aching, tingling, burning, stinging, itching, or cramping. Patients can describe heaviness and aching in the legs with prolonged standing. The pain is usually localized to the calf or along the varicose veins and is relieved by walking or lying down with the leg elevated. If the leg pain is unrelieved by leg elevation, especially overnight, other etiologies such as PAD should be suspected. Patients with obstruction of the deep venous system can experience venous claudication, a mild aching sensation at rest that becomes an intense cramping-type sensation in the calf with ambulation. The patient might have to stop and allow venous congestion to resolve.

The cutaneous manifestation of CVI is characterized by brownish pigmentation, especially along the perimalleolar area, caused by hemosiderin deposits in the skin (Figure 56-12). Some patients can have a reddish purple hue from venous engorgement and obstruction. The secondary weepy pruritus that occurs can induce scratching, eventually leading to eczematous stasis dermatitis, recurrent cellulitis, ulceration, and obliteration of cutaneous lymphatics. Eczema is usually seen in uncontrolled CVI but can be caused by sensitization to local therapy. Patients with severe CVI can develop lipodermatosclerosis and/or atrophie blanche. Lipodermatosclerosis is caused by chronic inflammation and fibrosis of the skin and subcutaneous tissue of the lower leg, and at times is associated with Achilles tendon contracture resulting from scarring. Atrophie blanche is a localized, often circular, whitish atrophic skin surrounded by dilated capillaries and at times hyperpigmentation. It can be mistaken for scarring from healed ulcers (see Figure 56-12).

FIGURE 56-12 Patient with chronic venous insufficiency that has chronic venous stasis skin changes and venous ulceration. Note the atrophie blanche posterior to the ulcer.

Physiatrists should be familiar with the CEAP classification system, developed by the International Consensus Conference on Chronic Venous Disorders convened by the American Venous Forum.⁷ CEAP classification allows the physician to document the severity of clinical manifestations (C), etiology of the CVI (E), anatomic distribution of the venous system involved (A), and pathophysiologic mechanism (P) in one single classification. This allows uniform reporting of research and clinical documentation and can help direct diagnostic testing and the degree and intensity of therapeutic interventions. This was initially developed in 1994 and was revised in 2004. See Box 56-4 for clinical classifications used in CEAP.

Diagnostic Evaluation of Chronic Venous Insufficiency

Duplex ultrasound scanning has become the test of choice for evaluation of patients with CVI. It is safe, noninvasive, cost-effective, and reliable. Duplex ultrasound scanning is indicated in young patients who present with CVI and in patients with acute new-onset stasis dermatitis. Duplex scanning allows identification of any underlying unrecognized acute or subacute DVT, as well as the site and type of pathology causing the CVI (superficial vs. deep; reflux vs. reflux with obstruction).

Although duplex ultrasound is the preferred study to evaluate reflux and obstruction, plethysmography can be used to detect venous obstruction when it is suspected but not found on ultrasound examination. Additionally, impedance plethysmography is useful to assess efficiency of the calf muscle pump, the amount of reflux, and degree of obstruction. Venography has also largely been replaced by duplex ultrasound but is still an important technique to evaluate venous anatomy before endovenous therapy or deep vein reconstruction. Computed tomography (CT) venography and magnetic resonance (MR) venography are not first-line examination techniques but do have an important role in certain patients.

Management of Chronic Venous Insufficiency

Treatment of CVI includes conservative, interventional, and surgical options. Approach to treatment depends on severity of the disease and the underlying pathology. Edema control by use of external compressive devices and limb elevation remains the first line of treatment for CVI and venous ulcers.

When limb elevation is used for edema control, patients should be instructed to elevate the limb above heart level. Periodic elevation of the leg 20 cm above heart level during the day has been shown to relieve edema by effectively lowering the hydrostatic pressure to nearly zero.

Compression stockings reduce superficial venous volume and venous hypertension, assist calf muscle pump, and help prevent transcapillary leakage of fluid into the interstitial tissue. A variety of external compression devices are available, including graduated elastic stockings, elastic bandages, paste gauze boots, Unna boots, multilayer wraps, and dressings. All of these are designed to allow ambulation during treatment. Compression bandages such as ace wraps are the simplest and least expensive. Disadvantages include difficulty in wrapping, maintaining correct position, and loss of elasticity with washing. Despite these disadvantages, elastic wrap bandages are useful in elderly patients who cannot don tight stockings and in patients with abnormally contoured limbs.

Below-the-knee custom-fitted graduated elastic compression stockings are better tolerated and are the treatment of choice for many cases of CVI. For CVI patients with diabetic neuropathy, closed toe stockings are recommended. Above-the-knee stockings are not indicated because high pressure is needed primarily around the ankle. They also tend to bind around the popliteal area. The stockings should be applied in the morning when there is minimal edema. Stockings should not be worn at night while sleeping because they can gather at the top and cause proximal vasoconstriction.

Contraindications for compression therapy include arterial insufficiency with ABI of less than 0.6, ankle pressure less than 60 mm Hg, active skin disease, or allergy to any of the stocking components. Stockings are available in many brands with several gradients of compression. Examples include Jobst, Sigvaris, Juzo, and Barton Carey.

The optimal pressure required to overcome the abnormal hemodynamics caused by ambulatory venous hypertension remains a matter of debate. Physiologically, intravenous pressure in the leg vein reflects the weight of the blood column between the site of measurement and the right atrium. In the supine position, the leg vein venous pressure will be between 10 and 20 mm Hg. Studies have shown that an external pressure of 10 to 20 mm Hg narrows the leg veins in the supine position and can totally occlude them at higher pressures of 20 to 25 mm Hg. Thromboembolic stockings exert a pressure between 14 and 20 mm Hg. During standing, intravenous pressure in the lower leg veins will be around 60 mm Hg, depending on the height of the individual. An external pressure of 35 to 40 mm Hg has been shown to narrow the veins in the standing position, and 60 mm Hg will totally occlude the veins in the standing position. For mild disease and those with underlying arterial disease, compression stockings with 20 to 30 mm Hg pressure are indicated. For moderate to severe disease, 30 to 40 mm Hg pressure is appropriate. The stockings need to be replaced every 4 to 6 months because they tend to lose elasticity and pressure over time. Compression stockings are difficult to don and might require use of a zipper. Use of an inner silk liner fitted on the toe, kitchen gloves, or a “butler device” (which holds the stockings open) might make it easier to don the stockings.³⁵

Intermittent pneumatic compression (IPC) devices can improve microcirculatory changes seen in CVI and can be used as an adjunctive device for edema control and ulcer healing. These are useful in patients with significant edema and morbid obesity. IPC devices provide sequential gradient compression and might be useful in treatment of refractory venous ulcers that do not heal with ambulatory compression alone and in patients who cannot tolerate compression bandages or stockings.³⁹ Contraindications for IPC include DVT, active infection, uncontrolled congestive cardiac failure, and significant arterial insufficiency.

Medications for Chronic Venous Insufficiency

Short-term use of diuretics helps reduce edema but generally does not help with the pain or discomfort associated with CVI. Use of systemic antibiotics should be limited to cases having obvious infection of the ulcer, periwound cellulitis, and septicemia. Aspirin, 325 mg/day, has been shown to provide additional benefit to compression therapy.¹⁸ Pentoxifylline, 1200 mg/day, also appears to promote healing when used in conjunction with compression therapy.¹⁹ Venotrophic drugs, which improve venous tone and flow, are used in European countries for treatment of CVI. Flavonoids and horse chestnut seed extract fall into this category. Horse chestnut seed extract (Aescin), an herbal remedy, has been shown to decrease pain, pruritus, and edema by preventing leukocyte activation and increasing venous tone and venous flow when used in conjunction with compression therapy.^2,4,48 A Cochrane Review of 17 randomized controlled trials has shown short-term improvement in signs and symptoms of CVI with use of horse chestnut seed extract; however, it is not approved by the U.S. Food and Drug Administration at this time.

Sclerotherapy for Chronic Venous Insufficiency

Sclerotherapy is used for treatment of venous telangiectasia, spider veins, and small varicose veins. It is helpful in reducing pain and discomfort and improving cosmesis. With sclerotherapy, a sclerosant that irritates the endothelial lining is injected into the vein followed by 3 to 6 weeks of compression until the vein walls are fused. Complications are rare and usually minor and include hyperpigmentation, blistering, urticaria, and edema. For patients who have isolated superficial telangiectasia, laser therapy is another option.

Surgery for Chronic Venous Insufficiency

For management of large symptomatic varicose veins, surgery is used alone or in conjunction with endovenous radiofrequency ablation, endovenous laser, or sclerotherapy. Removal or obliteration of the greater saphenous vein alone can resolve 90% of venous hypertension that is caused by superficial or perforator vein reflux. In the remaining 10%, ligation of incompetent perforator veins and valvuloplasty might also be needed.

Venous Ulceration

Ulceration is the disabling complication of CVI. Venous ulcers are most often large, irregular in shape, and have a flat wound edge with a shallow moist ruddy or beefy granulation base. The majority of venous ulcers are located along the medial or lateral aspect of the leg in the supramalleolar area (see Figure 56-12). Venous ulcer formation risk is highest when the ambulatory venous pressure is 80 mm Hg or greater.

Treatment of venous leg ulcers begins with meticulous local wound care and careful attention to the skin surrounding the ulcer. Local wound care should include sharp or enzymatic debridement for removal of nonviable tissue to decrease the bacterial bioburden, control bacterial colonization, and cleanse the wound. Optimal wound dressing should provide moisture and temperature balance. Many topical wound care products are available. Many are costly, and efficiency beyond standard compression therapy has not been demonstrated. Thomas and O’Donnell⁶⁵ conducted a systematic review of all randomized controlled trials published on wound dressings since 1997 through 2004 on treatment of venous ulcers and other chronic wounds. For uncomplicated wounds, they recommend treatment with occlusive dressings such as Tegasorb or Viscopaste because they provide constant mild rigid compression and a decreased frequency of dressing changes. Their review also supported use of Xenograft Oasis for noninfected wounds with some degree of granulation tissue and Apligraf for hard to heal large wounds.⁶⁵

Topical midpotency corticosteroids, such as triamcinolone 0.1% ointment, are helpful to reduce the inflammation and itching caused by stasis dermatitis in the surrounding skin. Secondary bacterial infection causing typical honey-colored crusting needs to be treated with appropriate antibiotics. Localized infection can be treated with silver-based wound dressings. Contact dermatitis is common and can be problematic in these patients, so they should be instructed not to apply over-the-counter antibiotics or other topical agents without the direction of a physician.

Compression therapy is the mainstay of treatment and is aimed at lessening the impact of the underlying venous insufficiency. The goal of compression therapy is to facilitate healing of stasis ulcers and prevent recurrences. Compression therapy promotes reasonably rapid healing, usually within 3 months except in patients who are elderly, obese, have coexisting arterial insufficiency, deep venous reflex, or long-standing large ulcers.

The most common methods of compression are Unna boot and multilayer compression bandages. Unna boots are made with a paste containing zinc oxide, gelatin, sorbitol, magnesium sulfate, and glycerin. Unna boots dry to a semirigid consistency when applied. The Unna boot is changed weekly or sooner if there is significant drainage or discomfort. The advantage of the Unna boot is minimal patient involvement while providing continued compression. Disadvantages are that some patients find it uncomfortable to wear, and it can cause contact dermatitis. The multilayer system Profore (Smith + Nephew United, London, UK) and Dyna-Flex Multi-layer compression system (Johnson & Johnson, New Brunswick, NJ) are better tolerated. Profore involves sequential application of (1) orthopedic wool wrap, which absorbs exudate and protects bony eminence; (2) crepe bandage, adding absorbency; (3) light-compression bandage, which is highly conformable to accommodate a difficult limb shape; and (4) a cohesive flexible bandage that applies pressure, maintaining effective levels of compression up to 1 week.⁸ This system provides 40 mm Hg pressure at the ankle in resting position, which decreases to 17 mm Hg below the knee. In one study using this therapy, 74% of 148 ulcerated limbs had ulcer healing by 12 weeks. Profore should not be used in patients with an ABI less than 0.8. Profore Lite should not be used in patients with an ABI less than 0.6. Circ-Aid is a legging orthosis and is another option available for compression. It provides inelastic rigid compression. Because its bands are adjustable, it is easier to don and is adjustable as the limb edema decreases.

Surgical treatment with skin grafting can be needed for ulcers that are large and do not heal. Once healing occurs, patients should be fitted with pressure gradient stockings. Patients should be educated about the permanent nature of their venous insufficiency and lifelong need for compliance with daily use of compression stocking. Skin biopsy can be needed in long-standing ulcers if another etiology, such as Kaposi sarcoma or Marjolin’s ulcer, is suspected.

Superficial Thrombophlebitis

Superficial thrombophlebitis is treated with elevation, superficial heat, and ambulation with 30 to 40 mm Hg compression stockings. Nonsteroidal antiinflammatorydrugs are useful in reducing pain and limiting local inflammation. More aggressive treatment is needed for patients with (1) superficial phlebitis involving the greater saphenous vein above the knee, (2) history of DVT, and (3) known irreversible risk factors. If there is evidence of involvement of the deep venous system by duplex ultrasound examination, the patient should be treated for DVT.

Epidemiology of Venous Thromboembolism

According to the Centers for Disease Control and Prevention data, the annual U.S. incidence of DVT and PE is 300,000 to 600,000 (of which 200,000 to 400,000 are PE). Nearly one third of patients who have PE die. VTE is primarily a disease of old age. The incidence increases exponentially with age, with a relative risk of 1.9 for each 10-year increase in age for both men and women. The overall male/female incidence ratio is 1.2:1. The incidence is higher in women in childbearing years. African Americans and whites have a higher incidence of VTE than Asians, Pacific Islanders, Hispanics, and Native Americans.²⁵ Two thirds of VTE cases are associated with recent hospitalizations, and half of all DVT episodes occur in hospitalized or nursing home residents.⁵⁴ Approximately 90% of DVTs occur in lower limbs; however, with frequent instrumentation and improved diagnostic testing, it is increasingly being recognized in upper limbs as well. Rarely, DVT occurs in cerebral sinuses, mesenteric arteries, and the retina.

In rehabilitation patient populations, the following incident rates of DVT have been reported in various studies:

Recurrence of DVT and PE is higher in the first 6 to 12 months, and cumulative recurrence rate can be as high as 24% at 5 years and 30% at 8 years after the initial episode.⁵⁰ Hansson et al.¹² in their study of 738 patients found a higher incidence of recurrence in patients with residual thrombus, idiopathic DVT, proximal DVT, cancer, history of thromboembolic events, and short duration of anticoagulant therapy. Patients with postoperative DVT had a lower recurrence rate in their study.

Pathogenesis of Venous Thromboembolism

Many factors, genetic and environmental, contribute to the development of DVT. Primary or idiopathic DVT occurs in the absence of recognized thrombotic risk factors, whereas secondary DVT occurs in the presence of known risk factors. Approximately 80% of inpatients with VTE and 30% of outpatients with confirmed DVT have been shown to have three or more risk factors. The Virchow’s Triad of (1) venous stasis, (2) vessel wall injury, and (3) variation in coagulability of the blood comprises the critically important contributors in the pathogenesis of DVT. (See Table 56-1 for risk factors that are associated with each of these contributors.) Each of these factors plays variable roles in individual patients.

Table 56-1 Risk Factors Associated With Virchow’s Triad

Thrombi usually begin to form at low flow sites, such as the deep veins of the calf, soleus sinuses, behind the cusps of venous valves, and at the entrance of tributary veins.⁶² Surgery of hip and knee, venous catheterization, and burns can cause vessel wall damage that initiates thrombus formation. Vascular endothelium is generally considered to be nonthrombogenic; however, when endothelium is damaged, platelets interact with subendothelial constituents and initiate thrombus formation with activation of coagulation factors. Venous thrombi consist of deposits of fibrin, red cells, and variable amount of platelets and leukocytes.¹⁶ Clearance of activated coagulation factors is prevented by venous stasis and facilitates interaction of thrombus with the vessel wall. The relative balance between activated coagulation and the thrombolytic system determines further propagation and dissolution of thrombus. It is fortunate that many small calf vein thrombi undergo rapid dissolution without therapy and rarely cause clinically significant PE. Although calf thrombi are regarded as an unusual source of symptomatic PE, they have been associated with high probability lung scans in up to 29% of patients with isolated calf vein thrombi.

Most clinically significant PE originates from DVT of the proximal lower limb (popliteal, femoral, or iliac veins).³⁶ Ninety percent of pulmonary emboli are associated with proximal lower limb venous thrombosis. Organization of large thrombi usually results in anatomic and functional changes in the vein. These changes include vein wall fibrosis, venous outflow obstruction, and valvular incompetence. These changes result in reflux and postthrombotic CVI. Recanalization of proximal venous thrombi occurs in fewer than 10% of patients and can take several months or more. The incidence of postthrombotic syndrome is 6 times higher in patients with recurrent thrombosis.

History and Clinical Features of Venous Thromboembolism

The evaluation for suspected VTE begins with a careful history and physical examination. Relevant history in these patients includes the patient’s symptoms and assessment of potential risk factors. No single physical finding or combination of symptoms and signs is sufficiently accurate to clinically establish the diagnosis of VTE. Classic signs of edema, erythema, warmth, tenderness, and positive Homan’s sign are nonspecific and might not be always present. In fact, Homan’s sign can be present in 50% of those without DVT. DVT is confirmed in only 50% of thosewith leg pain, tenderness, and swelling, only 20% of those with leg pain and tenderness, and only 11% of those with isolated swelling. Patients can present with unilateral edema and tenderness confined to the calf muscle or along the distribution of the deep veins of medial thigh without any other signs. A 3-cm or greater difference in calf circumference 10 cm below the tibial tuberosity is associated with a high likelihood of having DVT.⁶¹ The clinical presentation varies with anatomic location and extent and degree of occlusion by the thrombus. Patients with obstructive iliofemoral thrombosis can present with a markedly swollen, cyanosed leg or with a white, cold leg if there is associated arterial spasm. In some cases the presenting signs and symptoms might include apprehension, diaphoresis, tachycardia, pleuritic chest pain, tachypnea, and light headedness caused by sudden hypotension. It is essential to confirm the clinical suspicion of venous thrombosis with objective testing. (See Table 56-2 for signs and symptoms of PE.)

Table 56-2 Symptoms and Signs of Pulmonary Embolism

Duplex Ultrasound for Deep Venous Thrombosis

Duplex ultrasound is the diagnostic test of choice for detection of DVT, replacing contrast venography and impedance plethysmography (Figure 56-13). Essential elements of duplex ultrasound examination include thrombus visualization, venous compressibility, and detection of venous flow. Noncompressibility of femoral and popliteal vein is diagnostic of proximal DVT. New thrombi are hypoechogenic, as opposed to chronic thrombi, which are echodense. The diagnostic sensitivity of duplex ultrasound for proximal DVT is high (94.2%) but is low (63.5%) for nonoccluding or isolated calf thrombi. Because there is 20% to 30% incidence of propagation of calf thrombi to the proximal venous system, repeat or serial ultrasound studies are recommended in 7 to 14 days for patients in whom a clinical concern remains despite initial negative results on examination.

FIGURE 56-13 Diagnostic and treatment algorithm for a patient with limb swelling. The primary consideration is to urgently evaluate for deep vein thrombosis, which can be life threatening. IVC, Inferior vena cava; LMWH, low-molecular-weight heparin.

Magnetic Resonance Venography

One advantage of MR venography is that it has 100% sensitivity in diagnosis of DVT proximal to the inguinal ligament. Ultrasound is not sensitive in detecting thrombi above the inguinal ligament. It is safe to use in pregnant women. Unlike duplex ultrasound, its results are independent of technologist experience. Disadvantages are cost, increased time, patient cooperation, and the fact that it cannot be used in patients with certain metal implants. Concern exists about systemic nephrogenic fibrosis with the use of gadolinium in patients with renal insufficiency.

D-Dimer Assay

d-dimer is a degradation product of cross-linked fibrin blood clot. Elevated levels of d-dimer occur with acute thrombosis, but this does not discriminate between physiologic (e.g., postoperative or posttrauma) or pathologic (e.g., deep vein) thrombi. d-dimer levels can be elevated in patients with cancer, recent trauma, surgery, sepsis, late pregnancy, hemorrhage, and many other medical conditions. d-dimer assay is a sensitive but nonspecific test. It offers greater benefit in outpatient testing than in the inpatient setting because inpatients more often tend to have the above-noted conditions that cause false-positive results. A study done in a rehabilitation inpatient population, however, showed d-dimer assay to be an effective screening test in suspected cases of DVT and can reduce the need for more expensive diagnostic workup.¹

Wells et al.^69,70 have developed a structured clinical prediction rule to standardize clinical assessment for patients with suspected PE and DVT. The assessment is based on the patient’s signs and symptoms, risk factors for VTE, and presence of alternative diagnosis. Patients are stratified into low, moderate, or high probability for DVT or PE based on the resultant score. A combination of Wells pretest probability score and quantitative d-dimer testing has been used to reduce the number of diagnostic tests performed in patients with suspected VTE in the outpatient setting, but this has not been validated for inpatients.

Ventilation Perfusion Scintigraphy

Ventilation perfusion scintigraphy was used as the first-line study before widespread use of spiral CT. A normal study can effectively rule out clinically important PE. One of the major disadvantages of ventilation perfusion scan is that the majority of patients with PE will have an intermediate or low probability scan requiring further testing. It still can be the first-line study for patients with allergy to contrast or renal insufficiency.

Spiral Computed Tomography

Spiral CT has emerged as the diagnostic study of choice for suspected PE. It is minimally invasive compared with pulmonary angiography but allows visualization of pulmonary vessels, parenchyma, pleura, and mediastinum. This helps identify alternative diagnosis in one fourth of patients, including atelectasis or pneumonia.

Pulmonary Angiography

Pulmonary angiography is costly, invasive, technically demanding, and has significant radiation exposure. It is considered the reference standard for diagnosis of PE but is no longer routinely used for the above reasons.

Duration of Anticoagulation Therapy

Patients with a first episode of VTE, with reversible time-limited risk factors or asymptomatic calf thrombi, should be treated for at least 3 months. Patients with idiopathic VTE need anticoagulation for 6 to 12 months. Patients with recurrent VTE, cancer, or genetic risk factors should receive anticoagulation beyond 12 months to lifetime.

Inferior Vena Cava Filter

Placement of an inferior vena cava filter is indicated for patients with acute DVT who have an absolute contraindication for anticoagulation. Contraindications to anticoagulation include acute hemorrhage, neurosurgery, or intracranial bleeding within 7 days, severe thrombocytopenia, heparin-induced thrombocytopenia within 90 days, and recent gastrointestinal bleed. Patients with recurrent VTE despite anticoagulation, pulmonary hypertension with reduced cardiac reserve, or free-floating iliofemoral thrombi are also candidates for inferior vena cava filter.³⁴

Ambulation After DVT

Historically, bed rest for several days was thought to be the safest for preventing PE in patients with proximal DVT. Recent literature has not supported this. In fact, recent studies have shown that early, and even immediate, ambulation after initiation of appropriate anticoagulation therapy in conjunction with compression therapy does not increase development of symptomatic PE.^45,66 Postthrombotic sequelae occur in almost half of all patients with proximal DVT. Initiation of early ambulation results in faster reduction of pain and swelling and less incidence of postthrombotic sequelae.

Adjunctive therapy with graduated below-knee stockings with 30 to 40 mm Hg pressure at the ankle is indicated after proximal DVT. Compression stockings have been shown to reduce the development of postthrombotic sequelae by approximately 50% when worn at least for the first 2 years.⁴⁹