Current Medical Diagnosis & Treatment 2015

12

Blood Vessel & Lymphatic Disorders

Christopher D. Owens, MD, MSc
Joseph H. Rapp, MD
Warren J. Gasper, MD
Meshell D. Johnson, MD

ATHEROSCLEROTIC PERIPHERAL VASCULAR DISEASE

OCCLUSIVE DISEASE: AORTA & ILIAC ARTERIES

 ESSENTIALS OF DIAGNOSIS

 Claudication: cramping pain or tiredness in the calf, thigh, or hip while walking.

 Diminished femoral pulses.

 Tissue loss (ulceration, gangrene) or rest pain.

 General Considerations

Occlusive atherosclerotic lesions developing in the extremities, or peripheral arterial disease (PAD), is evidence of a systemic atherosclerotic process. Pathologic changes of atherosclerosis may be diffuse, but flow-limiting stenoses occur segmentally. In the lower extremities, they classically occur in three anatomic segments: the aortoiliac segment, femoral-popliteal segment, and the infrapopliteal or tibial segment of the arterial tree. Each with its own population demographic, lesions in the distal aorta and proximal common iliac arteries classically occur in white male smokers aged 50–60 years. The aortoiliac disease may be the initial manifestation of systemic atherosclerosis. Disease progression may lead to complete occlusion of one or both common iliac arteries, which can precipitate occlusion of the entire abdominal aorta to the level of the renal arteries. Lesions affecting the external iliac arteries are less common as are lesions isolated to the aorta. This is particularly true of younger patients with isolated aortoiliac disease, ie, with no involvement of the more distal vessels of the lower extremities.

 Clinical Findings

  1. Symptoms and Signs

Pain occurs because blood flow cannot keep up with the increased demand of exercise. This pain, termed “claudication,” is typically described as severe and cramping and primarily occurs in the calf muscles. The pain from aorto-iliac lesions may extend into the thigh and buttocks with continued exercise and erectile dysfunction may occur from bilateral common iliac disease. Although generally reproducible, there is day-to-day variation in severity, thus the term, “intermittent claudication.” Rarely, patients complain only of weakness in the legs when walking, or simply extreme limb fatigue. The symptoms are relieved with rest. Femoral pulses are absent or very weak as are the distal pulses. A bruit may be heard over the aorta, iliac, or femoral arteries or over all three arteries.

  1. Doppler and Vascular Findings

The ratio of systolic blood pressure detected by Doppler examination at the ankle compared with the brachial artery (referred to as the ankle-brachial index [ABI]) is reduced to below 0.9 (normal ratio is 1.0–1.2); this difference is exaggerated by exercise. Both the dorsalis pedis and the posterior tibial artery are measured and the higher of the two artery pressures is used for calculation. Segmental waveforms or pulse volume recordings obtained by strain gauge technology through blood pressure cuffs demonstrate blunting of the arterial inflow throughout the lower extremity.

  1. Imaging

CT angiography (CTA) and magnetic resonance angiography (MRA) have largely replaced invasive angiography to determine the anatomic location of disease. Imaging is only required when symptoms require intervention, since a history and physical examination with vascular testing should appropriately identify the involved levels of the arterial tree.

 Treatment

  1. Conservative Care

A program that includes smoking cessation; risk factor reduction; weight loss; and consistent, moderate exercise will substantially improve walking distance. In patients with PAD, nicotine replacement therapy, bupropion, and varenicline have established benefits in smoking cessation. A strategy to motivate individuals to quit smoking uses “5Rs” Relevance of smoking cessation to the patient, discussing the Risk of smoking, Rewards of quitting (eg, cost savings, health benefits, sense of well-being), identification of Roadblocks, and importance of Repetition of a motivational intervention at all subsequent visits. A trial of phosphodiesterase inhibitors, such as cilostazol 100 mg orally twice a day, may be beneficial in approximately two-thirds of patients. Antiplatelet agents reduce overall cardiovascular morbidity but do not ameliorate symptoms. In the initial stages of a rehabilitation program, simply slowing the cadence of walking will allow patients to walk further without pain.

  1. Endovascular Techniques

When the atherosclerotic lesions are truly segmental, they can be effectively treated with angioplasty and stenting. This approach matches the results of surgery for single stenoses but both effectiveness and durability decreases with longer or multiple stenoses.

  1. Surgical Intervention

A prosthetic aorto-femoral bypass graft that bypasses the diseased segments of the aortoiliac system is a highly effective and durable treatment for this disease. Patients may be treated with a graft from the axillary artery to the femoral arteries (axillo-femoral bypass graft) or with a graft from the contralateral femoral artery (fem-fem bypass) when iliac disease is limited to one side. The axillo-femoral and femoral to femoral grafts have lower operative risk; however, they are less durable.

 Complications

The complications of the aorto-femoral bypass are those of any major abdominal reconstruction in a patient population that has a high prevalence of cardiovascular disease. Mortality is low (2–3%), but morbidity is higher and includes a 5–10% rate of myocardial infarction. While endovascular approaches are safer and the complication rate is 1% to 3%, they are less durable with extensive disease.

 Prognosis

Patients with isolated aortoiliac disease may have a further reduction in walking distance without intervention, but symptoms rarely progress to rest pain or threatened limb loss. Life expectancy is limited by their attendant cardiac disease with a mortality rate of 25–40% at 5 years.

Symptomatic relief is generally excellent after intervention. After aorto-femoral bypass, a patency rate of 90% at 5 years is common. Endovascular patency rates and symptom relief for patients with short stenoses are also good with 20–30% symptom return at 3 years. Recurrence rates following endovascular treatment of extensive disease is much higher.

 When to Refer

Patients with progressive reduction in walking distance in spite of risk factor modification and consistent walking programs and those with limitations that interfere with their activities of daily living should be referred for consultation to a vascular surgeon.

ACCF/AHA focused update of the guideline for the management of patients with peripheral artery disease (updating the 2005 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2011 Nov 1;124(18):2020–45. [PMID: 21959305]

Bachoo P et al. Endovascular stents for intermittent claudication. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD003228. [PMID: 20091540]

Le Faucheur A et al. Variability and short-term determinants of walking capacity in patients with intermittent claudication. J Vasc Surg. 2010 Apr;51(4):886–92. [PMID: 20347684]

Murphy TP et al; CLEVER Study Investigators. Supervised exercise versus primary stenting for claudication resulting from aortoiliac peripheral artery disease: six-month outcomes from the claudication: exercise versus endoluminal revascularization (CLEVER) study. Circulation. 2012 Jan 3;125(1): 130–9. [PMID: 22090168]

OCCLUSIVE DISEASE: SUPERFICIAL & COMMON FEMORAL & POPLITEAL ARTERIES

 ESSENTIALS OF DIAGNOSIS

 Cramping pain or tiredness in the calf with exercise.

 Reduced popliteal and pedal pulses.

 Foot pain at rest, relieved by dependency.

 Foot gangrene or ulceration.

 General Considerations

The superficial femoral artery is the artery most commonly occluded by atherosclerosis. The disease frequently occurs where the superficial femoral artery passes through the abductor magnus tendon in the distal thigh (Hunter canal). The common femoral artery and the popliteal artery are less commonly diseased but lesions in these vessels are debilitating, resulting in short-distance claudication. As with atherosclerosis of the aortoiliac segment, and PAD generally, these lesions are closely associated with a history of smoking.

 Clinical Findings

  1. Symptoms and Signs

Symptoms of intermittent claudication caused by lesions of the common femoral artery, superficial femoral artery, and popliteal artery are confined to the calf. Occlusion or stenosis of the superficial femoral artery at the adductor canal when the patient has good collateral vessels from the profunda femoris will cause claudication at approximately 2–4 blocks. However, with concomitant disease of the profunda femoris or the popliteal artery, much shorter distances may trigger symptoms. With short-distance claudication, dependent rubor of the foot with blanching on elevation may be present. Chronic low blood flow states will also cause atrophic changes in the lower leg and foot with loss of hair, thinning of the skin and subcutaneous tissues, and disuse atrophy of the muscles. With segmental occlusive disease of the superficial femoral artery, the common femoral pulsation is normal, but the popliteal and pedal pulses are reduced.

  1. Doppler and Vascular Findings

The ABI is reduced; levels below 0.5 suggest severe reduction in flow. ABI readings depend on arterial compression. Since the vessels may be calcified in diabetic patients and the elderly, ABIs can be misleading and must be accompanied by a waveform analysis. Pulse volume recordings with cuffs placed at the high thigh, mid thigh, calf, and ankle will delineate the levels of obstruction with reduced pressures and blunted waveforms.

  1. Imaging

Angiography, CTA, or MRA all adequately show the anatomic location of the obstructive lesions and are done only if revascularization is planned.

 Treatment

  1. Conservative Care

As with aortoiliac disease, conservative management has an important role for some patients, particularly those individuals with superficial femoral artery occlusion and good profunda femoris collateral vessels. For these patients conservative management with consistent exercise as noted above can result in excellent outcomes.

  1. Surgical Intervention
  2. Bypass surgery—Intervention is indicated if claudication is progressive, incapacitating, or interferes significantly with essential daily activities. Intervention is mandatory if there is rest pain or threatened tissue loss of the foot. The most effective and durable treatment for lesions of the superficial femoral artery is a femoral-popliteal bypass with autogenous saphenous vein. Synthetic material, usually polytetrafluoroethylene (PTFE), can be used, but these grafts do not have the durability of vein bypass.
  3. Endovascular surgery—Endovascular techniques are often used for lesions of the superficial femoral artery. Angioplasty may be combined with stenting. These techniques have lower morbidity than bypass surgery but also have lower rates of durability.

Endovascular therapy is most effective when the lesions are < 10 cm long and performed in patients who are undergoing aggressive risk factor modification. Drug-eluting stents may improve the patency of lower extremity revascularization.

  1. Thromboendarterectomy—Removal of the atherosclerotic plaque is limited to the lesions of the common femoral and the profunda femoris artery where bypass grafts and endovascular techniques have a more limited role.

 Complications

Open surgical procedures of the lower extremity, particularly long bypasses with vein harvest, have a risk of wound infection that is higher than in other areas of the body. Wound infection or seroma can occur in as many as 10–15% of cases. Myocardial infarction rates after open surgery are 5–10%, with a 1–4% mortality rate. Complication rates of endovascular surgery are 1–5%, making these therapies attractive despite their lower durability.

 Prognosis

The prognosis for motivated patients with isolated superficial femoral artery disease is excellent, and surgery is not recommended for mild or moderate claudication in these patients. However, when claudication significantly limits daily activity and undermines quality of life as well as overall cardiovascular health, intervention may be warranted. All interventions require close postprocedure follow-up with repeated ultrasound surveillance so that any recurrent narrowing can be treated promptly to prevent complete occlusion. The reported patency rate of bypass grafts of the femoral artery, superficial femoral artery, and popliteal artery is 65–70% at 3 years, whereas the patency of angioplasty is less than 50% at 3 years.

Because of the extensive atherosclerotic disease, including associated coronary lesions, 5-year mortality among patients with lower extremity disease can be as high as 50%, particularly with involvement of the infrapopliteal vessels (see below). However, with aggressive risk factor modification, substantial improvement in longevity has been reported.

 When to Refer

Patients with progressive symptoms, short distance claudication, rest pain, or any ulceration should be referred to a peripheral vascular specialist.

Bradbury AW et al; BASIL trial Participants. Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial: analysis of amputation free and overall survival by treatment received. J Vasc Surg. 2010 May;51(5 Suppl):18S–31S. [PMID: 20435259]

Conte MS. Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) and the (hoped for) dawn of evidence-based treatment for advanced limb ischemia. J Vasc Surg. 2010 May;51(5 Suppl):69S–75S. [PMID: 20435263]

Dake MD et al; Zilver PTX Investigators. Sustained safety and effectiveness of paclitaxel-eluting stents for femoropopliteal lesions: 2-year follow-up from the Zilver PTX randomized and single-arm clinical studies. J Am Coll Cardiol. 2013 Jun 18;61(24):2417–27. Erratum in: J Am Coll Cardiol. 2013 Aug 13;62(7):666. [PMID: 23583245]

Siracuse JJ et al. Results for primary bypass versus primary angioplasty/stent for intermittent claudication due to superficial femoral artery occlusive disease. J Vasc Surg. 2012 Apr;55(4):1001–7. [PMID: 22301210]

Torpy JM et al. JAMA patient page. Peripheral arterial disease. JAMA. 2009 Jan 14;301(2):236. [PMID: 19141772]

OCCLUSIVE DISEASE: TIBIAL & PEDAL ARTERIES

 ESSENTIALS OF DIAGNOSIS

 Severe pain of the forefoot that is relieved by dependency.

 Pain or numbness of the foot with walking.

 Ulceration or gangrene of the foot or toes.

 Pallor when the foot is elevated.

 General Considerations

Occlusive processes of the tibial arteries of the lower leg and pedal arteries in the foot occur primarily in patients with diabetes. There often is extensive calcification of the artery wall.

 Clinical Findings

  1. Symptoms and Signs

Unless there are associated lesions in the aortoiliac or femoral/superficial femoral artery segments, claudication may not occur. The gastrocnemius and soleus muscles may be supplied from collateral vessels from the popliteal artery; therefore, when disease is isolated to the tibial vessels, there may be foot ischemia without attendant claudication, and rest pain or ulceration may be the first sign of severe vascular insufficiency. Classically, ischemic rest pain is confined to the dorsum of the foot and is relieved with dependency; the pain does not occur with standing or sitting. It is severe and burning in character, and because it is only present when recumbent, it may awaken the patient from sleep. Because of the high incidence of neuropathy in these patients, it is important to differentiate rest pain from diabetic neuropathic dysesthesia. If the pain is relieved by simply dangling the foot over the edge of the bed, which increases blood flow to the foot, then the pain is due to vascular insufficiency. Leg night cramps (not related to ischemia) occur often in patients with peripheral artery disease and should not be confused with rest pain.

On examination, depending on whether associated proximal disease is present, there may or may not be femoral and popliteal pulses, but the pedal pulses will be absent. Dependent rubor may be prominent with pallor on elevation. The skin of the foot is generally cool, atrophic, and hairless.

  1. Doppler and Vascular Findings

The ABI may be quite low (in the range of 0.3 or lower), but ABIs may be falsely elevated because of the noncompressability of the calcified tibial vessels. Waveform analysis is important in these patients; a monophasic flow pattern denotes critically low flow. Segmental pulse volume recordings will show a fall-off in blood pressure between the calf and ankle.

  1. Imaging

MRA or angiography is often needed to delineate the anatomy of the tibial-popliteal segment. CTA is less helpful for detection of lesions in this location due to vessel calcification.

 Treatment

Good foot care may avoid ulceration, and most diabetic patients will do well with a conservative regimen. However, if ulcerations appear and there is no significant healing within 2–3 weeks and studies indicate poor blood flow, revascularization will be required. Poor blood flow or infrequent rest pain without ulceration is not an indication for revascularization. However, rest pain occurring nightly with monophasic waveforms requires revascularization to prevent threatened tissue loss.

  1. Bypass and Endovascular Techniques

Bypass with vein to the distal tibial or pedal arteries has been shown to be an effective mechanism to treat rest pain and heal gangrene or ischemic ulcerations of the foot. Because the foot often has relative sparing of vascular disease, these bypasses have had adequate patency rates (70% at 3 years). Fortunately, in nearly all series, limb salvage rates are much higher than patency rates.

Endovascular techniques are beginning to be used in the tibial vessels with modest results in short lesions, but bypass grafting remains the primary technique of revascularization.

  1. Amputation

Patients with rest pain and tissue loss are at high risk for amputation, particularly if revascularization cannot be done. Amputations of the second through fifth toes may have little or no effect on the mechanics of walking. However, removal of the first toe or a transmetatarsal amputation of all digits increases the energy required for walking by 5–10%. Unfortunately, the next level that can be successfully used for a prosthesis is at the below-knee level. The energy expenditure of walking is then increased by 50%. With an above-knee amputation, the energy required to ambulate may be increased as much as 100%. While there are good prosthetic alternatives for these patients, activity levels are limited after amputation, and there are issues relating to self-image. These factors combine to demand revascularization whenever possible to preserve the limb.

 Complications

The complications of intervention are similar to those listed for superficial femoral artery disease with evidence that the overall cardiovascular risk of intervention increases with decreasing ABI. The patients with critical limb ischemia require aggressive risk factor modification. Wound infection rates after bypass are higher if there is an open wound in the foot.

 Prognosis

Patients with tibial atherosclerosis have extensive atherosclerotic burden and a high prevalence of diabetes. Their prognosis without intervention is poor and complicated by the risk of amputation.

 When to Refer

Patients with diabetes and foot ulcers should be referred for a formal vascular evaluation if pedal pulses are reduced. Intervention may not be necessary but the severity of the disease will be quantified, which has implications for future symptom development.

Hinchliffe RJ et al. A systematic review of the effectiveness of revascularization of the ulcerated foot in patients with diabetes and peripheral arterial disease. Diabetes Metab Res Rev. 2012 Feb;28(Suppl 1):179–217. [PMID: 22271740]

Scheinert D. A prospective randomized multicenter comparison of balloon angioplasty and infrapopliteal stenting with the sirolimus-eluting stent in patients with ischemic peripheral artery disease: 1-year results from the ACHILLES trial. J Am Coll Cardiol. 2012 Dec 4;60(22):2290–5. [PMID: 23194941]

Torpy JM et al. JAMA patient page. Peripheral arterial disease. JAMA. 2009 Jan 14;301(2):236. [PMID: 19141772]

ACUTE ARTERIAL OCCLUSION OF A LIMB

 ESSENTIALS OF DIAGNOSIS

 Sudden pain in an extremity.

 Generally associated with some element of neurologic dysfunction with numbness, weakness, or complete paralysis.

 Absent extremity pulses.

 General Considerations

Acute occlusion may be due to an embolus or to thrombosis of a diseased atherosclerotic segment. Emboli large enough to occlude proximal arteries in the lower extremities are almost always from the heart. Over 50% of the emboli from the heart go to the lower extremities, 20% to the cerebrovascular circulation, and the remainder to the upper extremities and mesenteric and renal circulation. Atrial fibrillation is the most common cause of cardiac thrombus formation; other causes are valvular disease or thrombus formation on the ventricular surface of a large anterior myocardial infarct.

Emboli from arterial sources such as arterial ulcerations or calcified excrescences are usually small and go to the distal arterial tree (toes).

The typical patient with primary thrombosis has had a history of claudication and now has an acute occlusion. If the stenosis has developed over time, collateral blood vessels will develop, and the resulting occlusion may only cause a minimal increase in symptoms.

 Clinical Findings

  1. Symptoms and Signs

The sudden onset of extremity pain, with loss or reduction in pulses, is diagnostic of acute arterial occlusion. This often will be accompanied by neurologic dysfunction, such as numbness or paralysis in extreme cases. With popliteal occlusion, symptoms may only affect the foot. With proximal occlusions, the whole leg may be affected. Signs of severe arterial ischemia include pallor, coolness of the extremity, and mottling. Impaired neurologic function progressing to anesthesia accompanied with paralysis suggests a poor prognosis.

  1. Doppler and Laboratory Findings

There will be little or no flow found with Doppler examination of the distal vessels. Imaging, if done, may show an abrupt cutoff of contrast with embolic occlusion. Blood work may show myoglobin and a metabolic acidosis.

  1. Imaging

Whenever possible, imaging should be done in the operating room because obtaining angiography, MRA, or CTA may delay revascularization and jeopardize the viability of the extremity. However, in cases with only modest symptoms and where light touch of the extremity is maintained, imaging may be helpful in planning the revascularization procedure.

 Treatment

Immediate revascularization is required in all cases of symptomatic acute arterial thrombosis. Evidence of neurologic injury, including loss of light touch sensation, indicates that collateral flow is inadequate to maintain limb viability and revascularization should be accomplished within 3 hours. Longer delays carry a significant risk of irreversible tissue damage. This risk approaches 100% at 6 hours.

  1. Heparin

As soon as the diagnosis is made, unfractionated heparin should be administered (5000–10,000 units) intravenously followed by a heparin infusion to maintain the activated partial thromboplastin time (aPTT) in therapeutic range (60–85 seconds) (12-18 units/kg/h). This helps prevent clot propagation and may also help relieve associated vessel spasm. There may be some reduction in symptoms with aggressive anticoagulation, but revascularization will still be required.

  1. Endovascular Techniques

Catheter-directed chemical thrombolysis into the clot with tissue plasminogen activator (TPA) may be done but often requires 24 hours or longer to fully lyse the thrombus. This approach can be taken only in patients with an intact neurologic examination who do not have absolute contraindications such as bleeding diathesis, gastrointestinal bleeding, intracranial trauma, or neurosurgery within the past 3 months. A sheath is used to advance a TPA-infusing catheter through the clot. Heparin is administered systemically to prevent thrombus formation around the sheath. Frequent vascular and access site examinations are required during the thrombolytic procedure to assess for improved vascular perfusion and to guard against the development of a hematoma.

  1. Surgical Intervention

General anesthesia is usually indicated; local anesthesia may be used in extremely high-risk patients if the exploration is to be limited to the common femoral artery. In extreme cases, it may be necessary to perform thrombo-embolectomy from the femoral, popliteal and even the pedal vessels to revascularize the limb. Devices to pulverize and aspirate clot and intraoperative thrombolysis with TPA are being used to improve outcomes.

 Complications

Complications of revascularization of an acutely ischemic limb can include severe metabolic acidosis, hyperkalemia, and cardiac arrest. In cases where several hours have elapsed but recovery of viable tissue may still be possible, significant levels of lactic acid, potassium, and other harmful agents may be released into the circulation during revascularization. Pretreatment of the patient with sodium bicarbonate prior to reestablishing arterial flow is required. Surgery in the presence of thrombolytic agents and heparin carries a high risk of postoperative wound hematoma.

 Prognosis

There is a 10–25% risk of amputation with acute arterial occlusion caused by an embolus, and a 25% or higher in-hospital mortality rate. Prognosis for acute thrombotic occlusion of an atherosclerotic segment is generally better because the collateral flow can maintain extremity viability. The longer term survival reflects the overall condition of the patient. In high-risk patients, an acute arterial occlusion is associated with a dismal prognosis.

OCCLUSIVE CEREBROVASCULAR DISEASE

 ESSENTIALS OF DIAGNOSIS

 Sudden onset of weakness and numbness of an extremity, aphasia, dysarthria, or unilateral blindness (amaurosis fugax).

 Bruit heard loudest in the mid neck.

 General Considerations

Unlike the other vascular territories, symptoms of occlusive cerebrovascular disease are predominantly due to emboli. Transient ischemic attacks (TIAs) are the result of small emboli, and the risk of additional emboli causing permanent deficits is high. One-third of all strokes may be due to arterial to arterial emboli. In the absence of atrial fibrillation, approximately 90% of these emboli originate from the proximal internal carotid artery, an area uniquely prone to the development of atherosclerosis. Lesions in the proximal great vessels of the aortic arch and the common carotid are far less common. Intracranial atherosclerotic lesions are less uncommon in the West but are the most common location of cerebrovascular disease in China.

 Clinical Findings

  1. Symptoms and Signs

Generally, the symptoms of a TIA last only a few seconds to minutes but may continue up to 24 hours. The most common lesions are in the cortex with both motor and sensory involvement. Emboli to the retinal artery cause unilateral blindness, which, when transient, is termed “amaurosis fugax.” Posterior circulation symptoms referable to the brainstem, cerebellum, and visual regions of the brain are due to atherosclerosis of the vertebral basilar systems and are much less common.

Signs of cerebrovascular disease include bruits in the mid-cervical area. However, there is poor correlation between the degree of stenosis and the presence of the bruit. Furthermore, absence of a bruit does not exclude the possibility of carotid stenosis. Nonfocal symptoms, such as dizziness and unsteadiness, seldom are related to cerebrovascular atherosclerosis.

  1. Imaging

Duplex ultrasonography is the imaging modality of choice with a high specificity and sensitivity for detecting and grading the degree of stenosis at the carotid bifurcation > 50% stenosis in a symptomatic patient and 80% in an asymptomatic patient require intervention. Mild to moderate disease (30–50% stenosis) indicates the need for ongoing surveillance and aggressive risk factor modification.

Excellent depiction of the full anatomy of the cerebrovascular circulation from arch to cranium can be obtained with either MRA or CTA. Each of these modalities may have false-positive or false-negative findings. Since the decision to intervene in cases of carotid stenosis depends on an accurate assessment of the degree of stenosis, it is recommended that at least two modalities be used to confirm the degree of stenosis. Diagnostic cerebral angiography is reserved for cases that cannot be resolved by MRA or CTA.

 Treatment

See Chapter 24 for a discussion of the medical management of occlusive cerebrovascular disease.

  1. Asymptomatic Patients

Large studies have shown a 5-year reduction in stroke rate from 11.5% to 5.0% with surgical treatment of > 60% asymptomatic carotid stenosis. Patients, therefore, with no neurologic symptoms but with carotid stenosis on imaging will benefit from carotid intervention if they are considered to be at low risk for intervention and their expected survival is > 5 years. The usual practice, however, is to only treat patients who have > 80% stenosis. Recommendation for intervention also presumes that the treating institution has a stroke rate in asymptomatic patients that is acceptable (< 3%). Patients with carotid stenosis that suddenly worsens are thought to have an unstable plaque and are at particularly high risk for embolic stroke.

  1. Symptomatic Patients

Large randomized trials have shown that patients with TIAs or strokes from which they have completely or nearly completely recovered will benefit from carotid intervention if the ipsilateral carotid artery has a stenosis of > 70%, and they are likely to derive benefit if the artery has a stenosis of 50–69%. In these situations, carotid endarterectomy (CEA) has been shown to have a durable effect in preventing further events.

 Complications

The most common complication from carotid intervention is cutaneous sensory or cranial nerve injury. However, the most dreaded complication is stroke due to embolization of plaque material during the procedure. The American Heart Association has recommended upper limits of acceptable combined morbidity and mortality for these interventions: 3% for asymptomatic, 5% for those with TIAs, and 7% for patients with previous stroke. Results that do not match these guidelines will jeopardize the therapeutic benefit of carotid intervention. In symptomatic patients, intervention should be planned as soon as possible. Delays increase the risk of a second event.

  1. Carotid Endarterectomy

In addition to stroke risk, CEA carries an 8% risk of transient cranial nerve injury (usually the vagus or hypoglossal nerve) and 1–2% risk of permanent deficits. There is also the risk of postoperative neck hematoma, which can cause acute compromise of the airway. Coronary artery disease exists as a comorbidity in most of these patients. Myocardial infarction rates after CEA are approximately 5%.

  1. Angioplasty and Stenting

Compared with CEA, the advantage of carotid angioplasty and stenting is the avoidance of both cranial nerve injury and neck hematoma. However, emboli are more common during carotid angioplasty and stenting in spite of the use of embolic protection devices during the procedure. The International Carotid Stenting Study showed increased stroke rates with carotid angioplasty and stenting in symptomatic patients while the Carotid Revascularization Endarterectomy versus Stent Trial (CREST) showed similar overall morbidity with higher myocardial infarction rates with CEA and higher stroke rates with carotid angioplasty and stenting. In cases of restenosis after previous carotid intervention, carotid angioplasty and stenting is an excellent choice since the risk of embolization is low and the risk of cranial nerve injury with surgery is high.

 Prognosis

Prognosis for patients with carotid stenosis who have had a TIA or small stroke is poor without treatment; 25% of these patients will have a stroke with most of the events occurring early in follow-up. Patients with carotid stenosis without symptoms have an annual stroke rate of just over 2% even with risk factor modification and antiplatelet agents. Prospective ultrasound screening is recommended in asymptomatic patients with known carotid stenosis because approximately 10% of asymptomatic patients have evidence of plaque progression in a given year. Concomitant coronary artery disease is common and is an important factor in these patients both for perioperative risk and long-term prognosis. Aggressive risk factor modification should be prescribed for patients with cerebrovascular disease regardless of planned intervention.

 When to Refer

Asymptomatic or symptomatic patients with a carotid stenosis of < 80% and patients with carotid stenosis of < 50% stenosis with symptoms of a TIA or stroke should be referred to a vascular specialist.

Brott TG et al; CREST Investigators. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med. 2010 Jul 1;363(1):11–23. [PMID: 20505173]

Hussain MS et al. Symptomatic delayed reocclusion after initial successful revascularization in acute ischemic stroke. J Stroke Cerebrovasc Dis. 2010 Jan;19(1):36–9. [PMID: 20123225]

International Carotid Stenting Study investigators;Ederle J et al. Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial. Lancet. 2010 Mar 20;375(9719):985–97. [PMID: 20189239]

VISCERAL ARTERY INSUFFICIENCY (Intestinal Angina)

 ESSENTIALS OF DIAGNOSIS

 Severe postprandial abdominal pain.

 Weight loss with a “fear of eating.”

 Acute mesenteric ischemia: severe abdominal pain yet minimal findings on physical examination.

 General Considerations

Acute visceral artery insufficiency results from either embolic occlusion or primary thrombosis of at least one major mesenteric vessel. Ischemia can also result from nonocclusive mesenteric vascular insufficiency, which is generally seen in patients with low flow states, such as heart failure, or hypotension. A chronic syndrome occurs when there is adequate perfusion for the viscera at rest but ischemia occurs with severe abdominal pain when flow demands increase with feeding. Because of the rich collateral network in the mesentery, generally at least two of the three major visceral vessels (celiac, superior mesenteric, inferior mesenteric arteries) are affected before symptoms develop. Ischemic colitis, a variant of mesenteric ischemia, usually occurs in the distribution of the inferior mesenteric artery. The intestinal mucosa is the most sensitive to ischemia and will slough if underperfused. The clinical presentation is similar to inflammatory bowel disease. Ischemic colitis can occur after aortic surgery, particularly aortic aneurysm resection or aortofemoral bypass for occlusive disease, when there is sudden reduction in blood flow to the inferior mesenteric artery.

 Clinical Findings

  1. Symptoms and Signs
  2. Acute intestinal ischemia—Patients with primary visceral arterial thrombosis often give an antecedent history consistent with chronic intestinal ischemia. The key finding with acute intestinal ischemia is severe, steady epigastric and periumbilical pain with minimal or no findings on physical examination of the abdomen because the visceral peritoneum is severely ischemic or infarcted and theparietal peritoneum is not involved. A high white cell count, lactic acidosis, hypotension, and abdominal distention may aid in the diagnosis.
  3. Chronic intestinal ischemia—Patients are generally over 45 years of age and may have evidence of atherosclerosis in other vascular beds. Symptoms consist of epigastric or periumbilical postprandial pain lasting 1–3 hours. To avoid the pain, patients limit food intake and may develop a fear of eating. Weight loss is universal.
  4. Ischemic colitis—Characteristic symptoms are left lower quadrant pain and tenderness, abdominal cramping, and mild diarrhea, which is often bloody.
  5. Imaging and Colonoscopy

Contrast-enhanced CT is highly accurate at determining the presence of ischemic intestine. In patients with acute or chronic intestinal ischemia, a CTA or MRA can demonstrate narrowing of the proximal visceral vessels. In acute intestinal ischemia from a nonocclusive low flow state, angiography is needed to display the typical “pruned tree” appearance of the distal visceral vascular bed. Ultrasound scanning of the mesenteric vessels may show proximal obstructing lesions in laboratories that have experience with this technique.

In patients with ischemic colitis, colonoscopy may reveal segmental ischemic changes, most often in the rectal sigmoid and splenic flexure where collateral circulation may be poor.

 Treatment

A high suspicion of acute intestinal ischemia dictates immediate exploration to determine bowel viability. If the bowel remains viable, bypass can be done either from the supra-celiac aorta or common iliac artery to the celiac and the superior mesentery artery. In cases where bowel viability is questionable or bowel resection will be required, the bypass can be done with autologous vein, or with cryopreserved allografts in order to avoid the use of prosthetic conduits in a potentially contaminated field.

In chronic intestinal ischemia, angioplasty and stenting of the proximal vessel may be beneficial depending on the anatomy of the stenosis. Should an endovascular solution not be available, an aorto-visceral artery bypass is the preferred management. The long-term results are highly durable. Visceral artery endarterectomy is reserved for cases with multiple lesions where bypass would be difficult.

The mainstay of treatment of ischemic colitis is maintenance of blood pressure and perfusion until collateral circulation becomes well established. The patient must be monitored closely for evidence of perforation, which will require resection.

 Prognosis

The combined morbidity and mortality rates are 10–15% from surgical intervention in these debilitated patients. However, without intervention both acute and chronic intestinal ischemia are uniformly fatal. Adequate collateral circulation usually develops in those who have ischemic colitis, and the prognosis for this entity is better than chronic intestinal ischemia.

 When to Refer

Any patient in whom there is a suspicion of intestinal ischemia should be urgently referred for imaging and possible intervention.

Acosta S. Epidemiology of mesenteric vascular disease: clinical implications. Semin Vasc Surg. 2010 Mar;23(1):4–8. [PMID: 20298944]

Cangemi JR et al. Intestinal ischemia in the elderly. Gastroenterol Clin North Am. 2009 Sep;38(3):527–40. [PMID: 19699412]

Gupta PK et al. Morbidity and mortality after bowel resection for acute mesenteric ischemia. Surgery. 2011 Oct;150(4):779–87. [PMID: 22000191]

ACUTE MESENTERIC VEIN OCCLUSION

The hallmarks of acute mesenteric vein occlusion are postprandial pain and evidence of a hypercoagulable state. Acute mesenteric vein occlusion presents similarly to the arterial occlusive syndromes but is much less common. Patients at risk include those with a systemic hypercoagulable state, such as that observed with paroxysmal nocturnal hemoglobinuria or protein C, protein S, antithrombin deficiencies, or the JAK2 mutation. These lesions are difficult to treat surgically, and thrombolysis is the mainstay of therapy. Aggressive long-term anticoagulation is required for these patients.

NONATHEROSCLEROTIC VASCULAR DISEASE

THROMBOANGIITIS OBLITERANS (Buerger Disease)

 ESSENTIALS OF DIAGNOSIS

 Typically occurs in male cigarette smokers.

 Distal extremities involved with severe ischemia, progressing to tissue loss.

 Thrombosis of the superficial veins may occur.

 Amputation will be necessary unless the patient stops smoking.

 General Considerations

Buerger disease is a segmental, inflammatory, and thrombotic process of the distal most arteries and occasionally veins of the extremities. Pathologic examination reveals arteritis in the affected vessels. The cause is not known but it is rarely seen in nonsmokers. Arteries most commonly affected are the plantar and digital vessels of the foot and lower leg. In advanced stages, the fingers and hands may become involved. While Buerger disease was once common, its incidence has decreased dramatically.

 Clinical Findings

  1. Symptoms and Signs

Buerger disease may be initially difficult to differentiate from routine peripheral vascular disease, but in most cases, the lesions are on the toes and the patient is younger than 40 years old. The observation of superficial thrombophlebitis may aid the diagnosis. Because the distal vessels are usually affected, intermittent claudication is not common with Buerger disease, but rest pain, particularly pain in the distal most extremity (ie, toes), is frequent. This pain often progresses to tissue loss and amputation, unless the patient stops smoking. The progression of the disease seems to be intermittent with acute and dramatic episodes followed by some periods of remission.

  1. Imaging

MRA or invasive angiography can demonstrate the obliteration of the distal arterial tree typical of Buerger disease.

 Differential Diagnosis

In atherosclerotic peripheral vascular disease, the onset of tissue ischemia tends to be less dramatic than in Buerger disease, and symptoms of proximal arterial involvement, such as claudication, predominate.

Symptoms of Raynaud disease may be difficult to differentiate from Buerger disease. Repetitive atheroemboli may also mimic Buerger disease and may be difficult to differentiate. It may be necessary to image the proximal arterial tree to rule out sources of arterial microemboli.

 Treatment

Smoking cessation is the mainstay of therapy and will halt the disease in most cases. As the distal arterial tree is occluded, revascularization is not possible. Sympathectomy is rarely effective.

 Prognosis

If smoking cessation can be achieved, the outlook for Buerger disease may be better than in patients with premature peripheral vascular disease. If smoking cessation is not achieved, then the prognosis is generally poor, with amputation of both lower and upper extremities the eventual outcome.

Abeles AM et al. Thromboangiitis obliterans successfully treated with phosphodiesterase type 5 inhibitors. Vascular. 2013 Sep 2. [Epub ahead of print] [PMID: 24000082]

Dargon PT et al. Buerger’s disease. Ann Vasc Surg. 2012 Aug;26(6):871–80. [PMID: 22284771]

ARTERIAL ANEURYSMS

ABDOMINAL AORTIC ANEURYSMS

 ESSENTIALS OF DIAGNOSIS

 Most aortic aneurysms are asymptomatic until rupture.

 Abdominal aortic aneurysms measuring 5 cm are palpable in 80% of patients.

 Back or abdominal pain with aneurysmal tenderness may precede rupture.

 Rupture is catastrophic; hypotension; excruciating abdominal pain that radiates to the back.

 General Considerations

Dilatation of the infrarenal aorta is a normal part of aging. The aorta of a healthy young man measures approximately 2 cm. An aneurysm is considered present when the aortic diameter exceeds 3 cm, but aneurysms rarely rupture until their diameter exceeds 5 cm. Abdominal aortic aneurysms are found in 2% of men over 55 years of age; the male to female ratio is 4:1. Ninety percent of abdominal atherosclerotic aneurysms originate below the renal arteries. The aneurysms usually involve the aortic bifurcation and often involve the common iliac arteries.

Inflammatory aneurysms are an unusual variant. These have an inflammatory peel (similar to the inflammation seen with retroperitoneal fibrosis) that surrounds the aneurysm and encases adjacent retroperitoneal structures, such as the duodenum and, occasionally, the ureters.

 Clinical Findings

  1. Symptoms and Signs
  2. Asymptomatic—Although 80% of 5-cm infrarenal aneurysms are palpable on routine physical examination, most aneurysms are discovered as incidental findings on ultrasound or CT imaging during the evaluation of unrelated abdominal symptoms.
  3. Symptomatic—
  4. PAIN—Aneurysmal expansion may be accompanied by pain that is mild to severe midabdominal discomfort often radiating to the lower back. The pain may be constant or intermittent and is exacerbated by even gentle pressure on the aneurysm sack. Pain may also accompany inflammatory aneurysms. Most aneurysms have a thick layer of thrombus lining the aneurysmal sac, but embolization to the lower extremities is rarely seen.
  5. RUPTUREThe sudden escape of blood into the retroperitoneal space causes severe pain, a palpable abdominal mass, and hypotension. Free rupture into the peritoneal cavity is a lethal event.
  6. Laboratory Findings

In acute cases of a contained rupture, the hematocrit may be normal, since there has been no opportunity for hemodilution.

Patients with aneurysms may also have such cardiopulmonary diseases as coronary artery disease, carotid disease, renal impairment, and emphysema, which are typically seen in elderly men who smoke. Preoperative testing may indicate the presence of these comorbid conditions, which increase the risk of intervention.

  1. Imaging

Abdominal ultrasonography is the diagnostic study of choice for initial screening for the presence of an aneurysm. In approximately three-quarters of patients with aneurysms, curvilinear calcifications outlining portions of the aneurysm wall may be visible on plain films of the abdomen or back. CT scans provide a more reliable assessment of aneurysm diameter and should be done when the aneurysm nears the diameter threshold (5.5 cm) for treatment. Contrast-enhanced CT scans show the arteries above and below the aneurysm. The visualization of this vasculature is essential for planning repair.

Once an aneurysm is identified, routine follow-up with ultrasound will determine size and growth rate. The frequency of imaging depends on aneurysm size ranging from every 2 years for small (< 4 cm aneurysms) to every 6 months for aneurysms at or approaching 5 cm. When an aneurysm measures approximately 5 cm, a CTA with contrast should be done to more accurately assess the size of the aneurysm and define the anatomy.

 Screening

Data support the use of abdominal ultrasound to screen 65- to 74-year-old men, but not women, who have a history of smoking. Repeated screening does not appear to be needed if the aorta shows no enlargement.

 Treatment

  1. Elective Repair

In general, elective repair is indicated for aortic aneurysms > 5.5 cm in diameter or aneurysms that have undergone rapid expansion (> 0.5 cm in 6 months). Symptoms such as pain or tenderness may indicate impending rupture and require urgent repair regardless of the aneurysm’s diameter.

  1. Aneurysmal Rupture

A ruptured aneurysm is a lethal event. Approximately half the patients exsanguinate prior to reaching a hospital. In the remainder, bleeding may be temporarily contained in the retroperitoneum (contained rupture), allowing the patient to undergo urgent surgery. However, only half of those patients will survive. Endovascular repair is available for urgent aneurysm repair in most major vascular centers, with the results offering some improvement over open repair for these critically ill patients.

  1. Inflammatory Aneurysm

The presence of periaortic inflammation (inflammatory aneurysm) is not an indication for surgical treatment, unless there is associated compression of retroperitoneal structures, such as the ureter. Interestingly, the inflammation that encases an inflammatory aneurysm recedes after either endovascular or open surgical aneurysm repair.

  1. Assessment of Operative Risk

Aneurysms appear to be a variant of systemic atherosclerosis. Patients with aneurysms have a high rate of coronary disease. A 2004 trial demonstrated minimal value in addressing stable coronary artery disease prior to aneurysm resection. However, in patients with significant symptoms of coronary disease, the coronary disease should be treated first. Aneurysm resection should follow shortly thereafter because there is a significant increased risk in aneurysm rupture after the coronary procedures. In patients with concomitant carotid stenosis, repairing symptomatic (but not asymptomatic) carotid disease prior to aneurysm resection is beneficial.

  1. Open Surgical Resection versus Endovascular Repair

In open surgical aneurysm repair, a graft is sutured to the non-dilated vessels above and below the aneurysm. This involves an abdominal incision, extensive dissection, and interruption of aortic blood flow. The mortality rate is low (2–5%) in centers that have a high volume for this procedure and when it is performed in good risk patients. Older, sicker patients may not tolerate the cardiopulmonary stresses of the operation. With endovascular repair, a stent-graft is used to line the aorta and exclude the aneurysm. The stent must be able to seal securely against the wall of the aorta above and below the aneurysm, thereby excluding blood from flowing into the aneurysm sac. The anatomic requirements to securely achieve aneurysm exclusion vary according to the performance characteristics of the specific stent-graft device. Most studies have found that endovascular aneurysm repair offers patients reduced operative morbidity and mortality as well as shorter recovery periods. However, long-term survival is equivalent between the two techniques. Patients who undergo endovascular repair require more repeat interventions and need to be monitored postoperatively, since there is a 10–15% incidence of continued aneurysm growth post endovascular repair.

  1. Thrombus in an Aneurysm

The presence of thrombus within the aneurysm is not an indication for anticoagulation.

 Complications

Myocardial infarction, the most common complication, occurs in up to 10% of patients who undergo open aneurysm repair. The incidence of myocardial infarction is substantially lower with endovascular repair. For routine infrarenal aneurysms, renal injury is unusual; however, when it does occur, or if the baseline creatinine is elevated, it is a significant complicating factor in the postoperative period. Respiratory complications are similar to those seen in most major abdominal surgery. Gastrointestinal hemorrhage, even years after aortic surgeries, suggests the possibility of graft enteric fistula; the incidence of this complication is higher when the initial surgery is performed on an emergency basis.

 Prognosis

The mortality rate for an open elective surgical resection is 1–5%, and the mortality rate for endovascular therapy is 0.5–2%. Of those who survive surgery, approximately 60% are alive at 5 years; myocardial infarction is the leading cause of death. The decision to repair aneurysms in high-risk patients has been made easier with the reduced perioperative morbidity and mortality of the endovascular approach.

Mortality rates of untreated aneurysms vary with aneurysm diameter. The mortality rate among patients with large aneurysms has been defined as follows: 12% annual risk of rupture with an aneurysm > 6 cm in diameter and a 25% annual risk of rupture in aneurysms of > 7 cm diameter. In general, a patient with an aortic aneurysm > 5.5 cm has a threefold greater chance of dying of a consequence of rupture of the aneurysm than of dying of the surgical resection.

At present, endovascular aneurysm repair may be less definitive than open surgical repair and requires close follow up with an imaging procedure. Device migration, component separation, limb thrombosis, or limb kinking are common reasons for repeat intervention. With complete exclusion of blood from the aneurysm sac, the pressure is lowered, which causes the aneurysm to shrink. An “endoleak” from the top or bottom of the graft (type 1) or through a graft defect (type 3) is associated with a persistent risk of rupture. Indirect leakage of blood through persistent lumbar and inferior mesenteric branches of the aneurysm (endoleak, type 2) produces an intermediate picture with somewhat reduced pressure in the sac, slow shrinkage, and low rupture risk. However, type 2 endoleak warrants close observation because aneurysm dilatation and rupture can occur.

 When to Refer

  • Any patient with a 4-cm aortic aneurysm or larger should be referred for imaging and assessment by a vascular specialist.
  • Urgent referrals should be made if the patient complains of pain and gentle palpation of the aneurysm confirms that it is the source, regardless of the aneurysmal size.

 When to Admit

Patients with signs of aortic rupture require emergent hospital admission.

De Bruin JL et al. Long-term outcome of open or endovascular repair of abdominal aortic aneurysm. N Engl J Med. 2010 May 20;362(20):1881–9. [PMID: 20484396]

Jackson RS et al. Comparison of long-term survival after open vs endovascular repair of intact abdominal aortic aneurysm among Medicare beneficiaries. JAMA. 2012 Apr 18;307(15):1621–8. [PMID: 22511690]

United Kingdom EVAR Trial Investigators;Greenhalgh RM et al. Endovascular versus open repair of abdominal aortic aneurysm. N Engl J Med. 2010 May 20;362(20):1863–71. [PMID: 20382983]

Wallace GA et al. Favorable discharge disposition and survival after successful endovascular repair of ruptured abdominal aortic aneurysm. J Vasc Surg. 2013 Jun;57(6):1495–502. [PMID: 23719035]

THORACIC AORTIC ANEURYSMS

 ESSENTIALS OF DIAGNOSIS

 Widened mediastinum on chest radiograph.

 With rupture, sudden onset chest pain radiating to the back.

 General Considerations

Most thoracic aortic aneurysms are due to atherosclerosis; syphilis is a rare cause. Disorders of connective tissue and Ehlers-Danlos and Marfan syndromes also are rare causes but have important therapeutic implications. Traumatic, false aneurysms, caused by partial tearing of the aortic wall with deceleration injuries, may occur just beyond the origin of the left subclavian artery. Less than 10% of aortic aneurysms occur in the thoracic aorta.

 Clinical Findings

  1. Symptoms and Signs

Most thoracic aneurysms are asymptomatic. When symptoms occur, they depend largely on the size and the position of the aneurysm and its rate of growth. Substernal back or neck pain may occur. Pressure on the trachea, esophagus, or superior vena cava can result in the following symptoms and signs: dyspnea, stridor, or brassy cough; dysphagia; and edema in the neck and arms as well as distended neck veins. Stretching of the left recurrent laryngeal nerve causes hoarseness. With aneurysms of the ascending aorta, aortic regurgitation may be present due to dilation of the aortic valve annulus. Rupture of a thoracic aneurysm is catastrophic because bleeding is rarely contained, allowing no time for emergent repair.

  1. Imaging

The aneurysm may be diagnosed on chest radiograph by the calcified outline of the dilated aorta. CT scanning is the modality of choice to demonstrate the anatomy and size of the aneurysm and to exclude lesions that can mimic aneurysms, such as neoplasms or substernal goiter. MRI can also be useful. Cardiac catheterization and echocardiography may be required to describe the relationship of the coronary vessels to an aneurysm of the ascending aorta.

 Treatment

Indications for repair depend on the location of dilation, rate of growth, associated symptoms, and overall condition of the patient. Aneurysms measuring 6 cm or larger may be considered for repair. Aneurysms of the descending thoracic aorta are treated routinely by endovascular grafting. Repair of arch aneurysms should be undertaken only if there is a skilled surgical team with an acceptable record of outcomes for these complex procedures. The availability of thoracic aortic endograft technique for descending thoracic aneurysms or experimental branched endovascular reconstructions for aneurysms involving the arch or visceral aorta (custom made grafts with branches to the vessels involved in the aneurysm) does not change the indications for aneurysm repair. Aneurysms that involve the proximal aortic arch or ascending aorta represent particularly challenging problems. Open surgery is usually required; however, it carries substantial risk of morbidity (including stroke, diffuse neurologic injury, and intellectual impairment) because interruption of arch blood flow is required.

 Complications

With the exception of endovascular repair for discrete saccular aneurysms of the descending thoracic aorta, the morbidity and mortality of thoracic repair is considerably higher than that for infra-renal abdominal aortic aneurysm repair. Paraplegia remains a devastating, complication. Most large series report approximately 4–10% rate of paraplegia following endovascular repair of thoracic aortic aneurysms. The spinal arterial supply is segmental through intercostal branches of the aorta with variable degrees of intersegmental connection. Therefore, the more extensive the aneurysm, the greater is the risk of paraplegia with resection. Prior infrarenal abdominal aortic surgery, subclavian or internal iliac artery stenosis, and hypotension all increase the paraplegia risk. Involvement of the aortic arch also increases the risk of stroke, even when the aneurysm does not directly affect the carotid artery.

 Prognosis

Generally, degenerative aneurysms of the thoracic aorta will enlarge and require repair to prevent death from rupture. However, stable aneurysms can be followed with CT scanning. Saccular aneurysms, particularly those distal to the left subclavian artery and the descending thoracic aorta, have had good results with endovascular repair. Resection of large complex aneurysms of the aortic arch requires a skilled surgical team for the major technical issues and should only be attempted in low-risk patients. Branched or fenestrated technology for endovascular grafting is becoming widely available and holds promise for reduced morbidity and mortality.

 When to Refer

Patients who are deemed to have a reasonable surgical risk with a 5–6 cm aneurysm should be considered for repair, particularly if the aneurysm involves the descending thoracic aorta.

 When to Admit

Any patient with chest or back pain with a known or suspected thoracic aorta aneurysm must be admitted to the hospital and undergo imaging studies to rule out the aneurysm as a cause of the pain.

Booher AM et al. Diagnosis and management issues in thoracic aortic aneurysm. Am Heart J. 2011 Jul;162(1):38–46.e1. [PMID: 21742088]

Gasper WJ et al. Assessing the anatomic applicability of the multibranched endovascular repair of thoracoabdominal aortic aneurysm technique. J Vasc Surg. 2013 Jun;57(6):1553–8. [PMID: 23395201]

Jonker FH et al. Meta-analysis of open versus endovascular repair for ruptured descending thoracic aortic aneurysm. J Vasc Surg. 2010 Apr;51(4):1026–32. [PMID: 20347700]

Jonker FH et al. Outcomes of endovascular repair of ruptured descending thoracic aortic aneurysms. Circulation. 2010 Jun 29;121(25):2718–23. [PMID: 20547930]

PERIPHERAL ARTERY ANEURSYMS

 ESSENTIALS OF DIAGNOSIS

 Widened, prominent pulses.

 Acute leg or foot pain and paresthesias with loss of distal pulses.

 High association of popliteal aneurysms with abdominal aortic aneurysms.

 General Considerations

Like aortic aneurysms, peripheral artery aneurysms are silent until critically symptomatic. However, unlike aortic aneurysms, the presenting manifestations are due to peripheral embolization and thrombosis. Popliteal artery aneurysms account for 70% of peripheral arterial aneurysms. Popliteal aneurysms may embolize repetitively over time and occlude distal arteries. Due to the redundant parallel arterial supply to the foot, ischemia does not occur until a final embolus occludes flow. Approximately one-third of patients will require an amputation. To prevent limb loss, popliteal artery aneurysms should be repaired if < 2 cm in diameter or if lined with thrombus at any size.

Primary femoral artery aneurysms are much less common. However, pseudoaneurysms of the femoral artery following arterial punctures for arteriography and cardiac catheterization occur with an incidence ranging from 0.05% to 6% of arterial punctures. Thrombosis and embolization are the main risks of femoral true or false aneurysms and, like popliteal aneurysms, should be repaired when < 2 cm in diameter.

 Clinical Findings

  1. Symptoms and Signs

The patient may be aware of a pulsatile mass when the aneurysm is in the groin, but popliteal aneurysms are often undetected by the patient and clinician. Rarely, peripheral aneurysms may produce symptoms by compressing the local vein or nerve. The first symptom may be due to ischemia of acute arterial occlusion. The symptoms range from sudden onset pain and paralysis to short distance claudication that slowly lessens as collateral circulation develops. Symptoms from recurrent embolization to the leg are often transient, if they occur at all. Sudden ischemia may appear in a toe or part of the foot, followed by slow resolution, and the true diagnosis may be elusive. The onset of recurrent episodes of pain in the foot, particularly if accompanied by cyanosis, suggests embolization and requires investigation of the heart and proximal arterial tree.

Because popliteal pulses are somewhat difficult to palpate even in normal individuals, a particularly prominent or easily felt pulse is suggestive of aneurysm and should be investigated by ultrasound. Since popliteal aneurysms are bilateral in 60% of cases, the diagnosis of thrombosis of a popliteal aneurysm is often aided by the palpation of a pulsatile aneurysm in the contralateral popliteal space. Approximately 50% of patients with popliteal aneurysms have an aneurysmal abdominal aorta.

  1. Imaging Studies

Duplex color ultrasound is the most efficient investigation to confirm the diagnosis of peripheral aneurysm, measure its size and configuration, and demonstrate mural thrombus. MRA or CTA are required to define the aneurysm and local arterial anatomy for reconstruction. Arteriography is not recommended because mural thrombus reduces the apparent diameter of the lumen on angiography. Patients with popliteal aneurysms should undergo ultrasonography to determine whether an abdominal aortic aneurysm is also present.

 Treatment

Surgery is indicated when an aneurysm is associated with any peripheral embolization, is < 2 cm, or a mural thrombus is present. Immediate or urgent surgery is indicated when acute embolization or thrombosis has caused acute ischemia. Intra-arterial thrombolysis may be done in the setting of acute ischemia, if examination (light touch) remains intact, suggesting that immediate surgery is not imperative. Bypass is generally performed. Endovascular exclusion of the aneurysm can be done but is reserved for high-risk patients. Acute pseudoaneurysms of the femoral artery due to arterial punctures can be successfully treated using ultrasound-guided compression. Open surgery with prosthetic interposition grafting is preferred for primary aneurysms of the femoral artery.

 Prognosis

The long-term patency of bypass grafts for femoral and popliteal aneurysms is generally excellent but depends on the adequacy of the outflow tract. Late graft occlusion is less common than in similar surgeries for occlusive disease.

 When to Refer

In addition to patients with symptoms of ischemia, any patient with a peripheral arterial aneurysm measuring 2 cm or with ultrasound evidence of thrombus within the aneurysm should be referred to prevent progression to limb-threatening ischemia.

Cross JE et al. Nonoperative versus surgical management of small (less than 3 cm), asymptomatic popliteal artery aneurysms. J Vasc Surg. 2011 Apr;53(4):1145–8. [PMID: 21439460]

AORTIC DISSECTION

 ESSENTIALS OF DIAGNOSIS

 Sudden searing chest pain with radiation to the back, abdomen, or neck in a hypertensive patient.

 Widened mediastinum on chest radiograph.

 Pulse discrepancy in the extremities.

 Acute aortic regurgitation may develop.

 General Considerations

Aortic dissection occurs when a spontaneous intimal tear develops and blood dissects into the media of the aorta. The tear probably results from the repetitive torque applied to the ascending and proximal descending aorta during the cardiac cycle; hypertension is an important component of this disease process. Type A dissection involves the arch proximal to the left subclavian artery, and type B dissectionoccurs in the proximal descending thoracic aorta typically just beyond the left subclavian artery. Dissections may occur in the absence of hypertension but abnormalities of smooth muscle, elastic tissue, or collagen are more common in these patients. Pregnancy, bicuspid aortic valve, and coarctation also are associated with increased risk of dissection.

Blood entering the intimal tear may extend the dissection into the abdominal aorta, the lower extremities, the carotid arteries or, less commonly, the subclavian arteries. Both absolute pressure levels and the pulse pressure are important in propagation of dissection. The aortic dissection is a true emergency and requires immediate control of blood pressure to limit the extent of the dissection. With type A dissection, which has the worse prognosis, death may occur within hours due to rupture of the dissection into the pericardial sac or dissection into the coronary arteries, resulting in myocardial infarction. Rupture into the pleural cavity is also possible. The intimal/medial flap of the aortic wall created by the dissection may occlude major aortic branches, resulting in ischemia of the brain, intestines, kidney, or extremities. Patients whose blood pressure is controlled and who survive the acute episode without complications may have long-term survival without surgical treatment.

 Clinical Findings

  1. Symptoms and Signs

Severe persistent chest pain of sudden onset radiating down the back or possibly into the anterior chest is characteristic. Radiation of the pain into the neck may also occur. The patient is usually hypertensive. Syncope, hemiplegia, or paralysis of the lower extremities may occur. Intestinal ischemia or renal insufficiency may develop. Peripheral pulses may be diminished or unequal. A diastolic murmur may develop as a result of a dissection in the ascending aorta close to the aortic valve, causing valvular regurgitation, heart failure, and cardiac tamponade.

  1. Electrocardiographic Findings

Left ventricular hypertrophy from long-standing hypertension is often present. Acute changes suggesting myocardial ischemia do not develop unless dissection involves the coronary artery ostium. Classically, inferior wall abnormalities predominate since dissection leads to compromise of the right rather than the left coronary artery. In some patients, the ECG may be completely normal.

  1. Imaging

A multiplanar CT scan is the immediate diagnostic imaging modality of choice; clinicians should have a low threshold for obtaining a CT scan in any hypertensive patient with chest pain and equivocal findings on ECG.

The CT scan should include both the chest and abdomen to fully delineate the extent of the dissected aorta. MRI is an excellent imaging modality for chronic dissections, but in the acute situation, the longer imaging time and the difficulty of monitoring patients in the MRI scanner make the CT scan preferable. Chest radiographs may reveal an abnormal aortic contour or widened superior mediastinum. Although transesophageal echocardiography (TEE) is an excellent diagnostic imaging method, it is generally not readily available in the acute setting.

 Differential Diagnosis

Aortic dissection is most commonly misdiagnosed as myocardial infarction or other causes of chest pain such as pulmonary embolization. Dissections may occur with minimal pain; branch vessel occlusion of the lower extremity can mimic arterial embolus.

 Treatment

  1. Medical

Aggressive measures to lower blood pressure should occur when an aortic dissection is suspected, even before the diagnostic studies have been completed. Treatment requires a simultaneous reduction of the systolic blood pressure to 100–120 mm Hg and pulse pressure. Beta-blockers have the most desirable effect of reducing the left ventricular ejection force that continues to weaken the arterial wall and should be first-line therapy. Labetalol, both an alpha- and beta-blocker, lowers pulse pressure and achieves rapid blood pressure control. Give 20 mg over 2 minutes by intravenous injection. Additional doses of 40–80 mg intravenously can be given every 10 minutes (maximum dose 300 mg) until the desired blood pressure has been reached. Alternatively, 2 mg/min may be given by intravenous infusion, titrated to desired effect. In patients who have asthma, bradycardia, or other conditions that necessitate the patient’s reaction to beta-blockers be tested, esmolol is a reasonable choice because of its short half-life. Give a loading dose of esmolol, 0.5 mg/kg intravenously over 1 minute followed by an infusion of 0.0025–0.02 mg/kg/min. Titrate the infusion to a goal heart rate of 60–70 beats/min. If beta-blockade alone does not control the hypertension, nitroprusside may be added as follows: 50 mg of nitroprusside in 1000 mL of 5% dextrose and water, infused at a rate of 0.5 mL/min; the infusion rate is increased by 0.5 mL every 5 minutes until adequate control of the pressure has been achieved. In patients with bronchial asthma, while there are no data supporting the use of the calcium-channel antagonists, diltiazem and verapamil are potential alternatives to treatment with beta-blocking drugs. Morphine sulfate is the appropriate drug to use for pain relief. Long-term medical care of patients should include beta-blockers in their antihypertensive regimen.

  1. Surgical Intervention

Urgent surgical intervention is required for all type A dissections. If a skilled cardiovascular team is not available, the patient should be transferred to an appropriate facility. The procedure involves grafting and replacing the diseased portion of the arch and brachiocephalic vessels as necessary. Replacement of the aortic valve may be required with reattachment of the coronary arteries.

Urgent surgery is required for type B dissections if there is aortic branch compromise resulting in malperfusion of the renal, visceral, or extremity vessels. The immediate goal of surgical therapy is to restore flow to the ischemic tissue, which is most commonly accomplished via a bypass. Endovascular stenting of the entry tear at the level of the subclavian artery may result in obliteration of the false lumen and restore flow into the branch vessel from the true lumen. The results, however, are unpredictable and should only be attempted with an experienced team. Evidence is emerging that long-term aortic-specific survival and delayed disease progression are improved with early thoracic stent graft repair.

 Prognosis & Follow-up

The mortality rate for untreated type A dissections is approximately 1% per hour for 72 hours and over 90% at 3 months. Mortality is also extremely high for untreated complicated type B dissections. The surgical and endovascular options for these patients also have significant morbidity and mortality. They are technically demanding and require an experienced team to achieve perioperative mortalities of < 10%. Patients with uncomplicated type B dissections whose blood pressure is controlled and who survive the acute episode without complications may have long-term survival without surgical treatment. Aneurysmal enlargement of the false lumen may develop in these patients despite adequate antihypertensive therapy. Yearly CT scans are required to monitor the size of the aneurysm. Indications for repair are determined by size (≥ 6 cm), similar to undissected thoracic aneurysms. Endovascular covering of the intimal tear in the acute setting may prevent this complication, but initial trials on the routine endovascular treatment of type B dissections have not shown an advantage for early intervention and therefore cannot be widely endorsed at this time.

 When to Admit

All patients with an acute dissection should be admitted. Any dissection involving the aortic arch (type A) should be immediately repaired. Acute type B dissections require repair only when there is evidence of rupture or major branch occlusion.

Nienaber CA et al. Endovascular repair of type B aortic dissection: long-term results of the randomized investigation of stent grafts in aortic dissection trial. Circ Cardiovasc Interv. 2013 Aug;6(4):407–16. [PMID: 23922146]

Nienaber CA et al. Strategies for subacute/chronic type B aortic dissection: the Investigation Of Stent Grafts in Patients with type B Aortic Dissection (INSTEAD) trial 1-year outcome. J Thorac Cardiovasc Surg. 2010 Dec;140(6 Suppl):S101–8. [PMID: 21092774]

Suzuki T et al; IRAD Investigators. Type-selective benefits of medications in treatment of acute aortic dissection (from the International Registry of Acute Aortic Dissection [IRAD]). Am J Cardiol. 2012 Jan 1;109(1):122–7. [PMID: 21944678]

VENOUS DISEASES

VARICOSE VEINS

 ESSENTIALS OF DIAGNOSIS

 Dilated, tortuous superficial veins in the lower extremities.

 May be asymptomatic or associated with aching discomfort or pain.

 Often hereditary.

 Increased frequency after pregnancy.

 General Considerations

Varicose veins develop in the lower extremities. Periods of high venous pressure related to prolonged standing or heavy lifting are contributing factors, but the highest incidence occurs in women after pregnancy. Varicosities develop in 15% of all adults.

The superficial veins are most commonly involved, typically the great saphenous vein and its tributaries, but the short saphenous vein (posterior lower leg) may also be affected. Distention of the vein prevents the valve leaflets from coapting, creating incompetence. Thus, dilation at any point along the vein leads to increased pressure and distention of the vein segment below that valve, which in turn causes progressive failure of the next lower valve and progressive venous reflux. Perforating veins that connect the deep and superficial systems may become incompetent, allowing blood to reflux into the superficial veins from the deep system through the incompetent perforators and increasing venous pressure and distention.

Secondary varicosities can develop as a result of obstructive changes and valve damage in the deep venous system following thrombophlebitis, or rarely as a result of proximal venous occlusion due to neoplasm or fibrosis. Congenital or acquired arteriovenous fistulas or venous malformations are also associated with varicosities and should be considered in young patients with varicosities.

 Clinical Findings

  1. Symptoms and Signs

Symptom severity is not correlated with the number and size of the varicosities; extensive varicose veins may produce no subjective symptoms, whereas minimal varicosities may produce many symptoms. Dull, aching heaviness or a feeling of fatigue of the legs brought on by periods of standing is the most common complaint.

Clinicians must be careful to identify symptoms of occlusive peripheral vascular disease, such as intermittent claudication or reduced pedal pulses, since occlusive arterial disease is usually a contraindication to the operative treatment of varicosities distal to the knee. Itching from venous stasis dermatitis may occur either above the ankle or directly overlying large varicosities.

Dilated, tortuous veins beneath the skin in the thigh and leg are generally visible upon standing, although in very obese patients palpation may be necessary to detect their presence and location. Some swelling is common but secondary tissue changes may be absent even in extensive varicosities. However, if the varicosities are of long duration, brownish pigmentation and thinning of the skin above the ankle may be present. The presence of a bruit or a thrill is useful in making the diagnosis of an associated arteriovenous fistula.

  1. Imaging

The identification of the source of venous reflux that feeds the symptomatic veins is necessary for effective surgical treatment. Duplex ultrasonography by a technician experienced in the diagnosis and localization of venous reflux is the test of choice for planning therapy. In most cases, reflux will arise from the greater saphenous vein.

 Differential Diagnosis

Primary varicose veins should be differentiated from those secondary to chronic venous insufficiency or obstruction of the deep veins with extensive swelling, fibrosis, and pigmentation, of the distal lower leg (post-thrombotic syndrome). Pain or discomfort secondary to arthritis, radiculopathy, or arterial insufficiency should be distinguished from symptoms associated with coexistent varicose veins. In adolescent patients with varicose veins, imaging of the deep venous system is important to exclude a congenital malformation or atresia of the deep veins. Surgical treatment of varicose veins in these patients is contraindicated because the varicosities may play a significant role in venous drainage of the limb.

 Complications

Thrombophlebitis within a varicose vein is uncommon. This presents as subacute to acute localized pain and palpable hardness at the site of the phlebitis. The process is self-limiting, has a low risk of embolization, and usually resolves within weeks. Rarely, the phlebitis extends to involve the greater saphenous vein. Predisposing conditions for thrombophlebitis include pregnancy, local trauma, or prolonged periods of sitting.

In older patients, superficial varicosities may bleed with even minor trauma. The amount of bleeding can be alarming as the pressure in the varicosity is high.

 Treatment

  1. Nonsurgical Measures

Nonsurgical treatment is effective. Elastic graduated compression stockings (20–30 mm Hg pressure) give external support to the veins. These stockings may be useful in early varicosities to prevent progression of disease. When elastic stockings worn during standing are combined with elevation of the legs when possible, good control can be maintained and the development of complications can often be avoided. This approach may be used in elderly patients, in those who refuse or wish to defer surgery, and in those with mild asymptomatic varicosities.

  1. Surgical Measures

Treatment with endovenous ablation (with either radiofrequency or laser) or, less commonly, with greater saphenous vein stripping is very effective for reflux arising from the greater saphenous vein. Less common sources of reflux include the lesser saphenous vein (for varicosities in the posterior calf), and incompetent perforator veins arising directly from the deep venous system in the thigh. Correction of reflux is performed at the same time as excision of the symptomatic varicose veins. Phlebectomy without correction of reflux results in a high rate of recurrent varicosities, as the uncorrected reflux progressively dilates adjacent veins. Concurrent reflux detected by ultrasonography in the deep system is not a contraindication to treatment of superficial reflux because the majority of deep vein dilatation is secondary to volume overload in this setting, which will resolve with correction of the superficial reflux.

  1. Compression Sclerotherapy

Sclerotherapy to obliterate and produce permanent fibrosis of the involved veins is generally reserved for the treatment of small varicose veins < 4 mm in diameter. Use of foam sclerotherapy can allow treatment of larger veins, although systemic embolization of the foam sclerosant may be a concern. The injection of the sclerosing solution into the varicosed vein is followed by a period of compression of the segment, resulting in obliteration of the vein. Complications such as phlebitis, tissue necrosis, or infection may occur, and vary in incidence with the skill of the clinician.

 Prognosis

Surgical correction of venous insufficiency (reflux) and excision of varicose veins provide excellent results. The 5-year success rate (as defined as lack of pain and recurrent varicosities) is 85–90%. Simple excision (phlebectomy) or injection sclerotherapy without correction of reflux is associated with higher rates of recurrence. Even after adequate treatment, secondary tissue changes, such as lipodermosclerosis, may persist.

 When to Refer

  • Absolute indications for referral for saphenous ablation include phlebitis and bleeding.
  • Pain and cosmetic concerns are responsible for the majority of referrals for ablation.

Di Nisio M et al. Treatment for superficial thrombophlebitis of the leg. Cochrane Database Syst Rev. 2012 Mar14;3:CD004982. [PMID: 22419302]

Figueiredo M et al. Results of surgical treatment compared with ultrasound-guided foam sclerotherapy in patients with varicose veins: a prospective randomised study. Eur J Vasc Endovasc Surg. 2009 Dec;38(6):758–63. [PMID: 19744867]

Gloviczki P et al. The care of patients with varicose veins and associated chronic venous diseases: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. J Vasc Surg. 2011 May;53(5 Suppl):2S–48S. [PMID: 21536172]

Hamdan A et al. JAMA patient page. Treatment of varicose veins. JAMA. 2013 Mar 27;309(12):1306. [PMID: 23532249]

Rasmussen LH et al. Randomised clinical trial comparing endovenous laser ablation with stripping of the great saphenous vein: clinical outcome and recurrence after 2 years. Eur J Vasc Endovasc Surg. 2010 May;39(5):630–5. [PMID: 20064730]

Subramonia S et al. Randomized clinical trial of radiofrequency ablation or conventional high ligation and stripping for great saphenous varicose veins. Br J Surg. 2010 Mar;97(3):328–36. [PMID: 20035541]

SUPERFICIAL VENOUS THROMBOPHLEBITIS

 ESSENTIALS OF DIAGNOSIS

 Induration, redness, and tenderness along a superficial vein, usually the saphenous vein.

 Induration, redness, and tenderness at the site of a recent intravenous line.

 Significant swelling of the extremity may not be seen.

 General Considerations

Short-term venous catheterization of superficial arm veins as well as the use of longer term peripherally inserted central catheter (PICC) lines are the most common cause of superficial thrombophlebitis. Intravenous catheter sites should be observed daily for signs of local inflammation and should be removed if a local reaction develops in the vein. Serious thrombotic or septic complications can occur if this policy is not followed.

Superficial thrombophlebitis may occur spontaneously, as in pregnant or postpartum women or in individuals with varicose veins or thromboangiitis obliterans; or it may be associated with trauma, as in the case of a blow to the leg or following intravenous therapy with irritating solutions. It also may be a manifestation of systemic hypercoagulability secondary to abdominal cancer such as carcinoma of the pancreas and may be the earliest sign of these conditions. Superficial thrombophlebitis may be associated with occult deep venous thrombosis (DVT) in about 20% of cases. Pulmonary emboli are exceedingly rare and occur from an associated DVT. (See Chapters 9 and Chapters 14 for discussion on Deep Venous Thrombosis.)

 Clinical Findings

In spontaneous superficial thrombophlebitis, the greater saphenous vein is most often involved. The patient usually experiences a dull pain in the region of the involved vein. Local findings consist of induration, redness, and tenderness along the course of a vein. The process may be localized, or it may involve most of the long saphenous vein and its tributaries. The inflammatory reaction generally subsides in 1–2 weeks; a firm cord may remain for a much longer period. Edema of the extremity is uncommon.

Localized redness and induration at the site of a recent intravenous line requires urgent attention. Proximal extension of the induration and pain with chills and high fever suggest septic phlebitis and requires urgent treatment.

 Differential Diagnosis

The linear rather than circular nature of the lesion and the distribution along the course of a superficial vein serve to differentiate superficial phlebitis from cellulitis, erythema nodosum, erythema induratum, panniculitis, and fibrositis. Lymphangitis and deep thrombophlebitis must also be considered.

 Treatment

For spontaneous thrombophlebitis if the process is well localized and not near the saphenofemoral junction, local heat, and nonsteroidal anti-inflammatory medications are usually effective in limiting the process. If the induration is extensive or is progressing toward the saphenofemoral junction (leg) or cephalo-axillary junction (arm), ligation and division of the vein at the junction of the deep and superficial veins is indicated.

Anticoagulation therapy is usually not required for focal processes. Prophylactic dose low-molecular-weight heparin or fondaparinux is recommended for 5 cm or longer superficial thrombophlebitis of the lower limb veins and full anticoagulation is reserved for disease that is rapidly progressing or there is concern for extension into the deep system.

Septic superficial thrombophlebitis is an intravascular abscess and requires urgent treatment with heparin (see Table 14–15) to limit additional thrombus formation as well as removal of the offending catheter in catheter-related infections (see Chapter 30). Staphylococcus aureus is the most common pathogen. Treat with antibiotics (eg, vancomycin, 15 mg/kg intravenously every 12 hours plus ceftriaxone, 1 g intravenously every 24 hours). If cultures are positive, therapy should be continued for 7–10 days or for 4–6 weeks if complicating endocarditis cannot be excluded. Other organisms, including fungi, may also be responsible. Surgical excision of the involved vein may also be necessary to control the infection.

 Prognosis

With spontaneous thrombophlebitis, the course is generally benign and brief. The prognosis depends on the underlying pathologic process. In patients with phlebitis secondary to varicose veins, recurrent episodes are likely unless correction of the underlying venous reflux and excision of varicosities is done. In contrast, the mortality from septic thrombophlebitis is 20% or higher and requires aggressive treatment. However, if the involvement is localized, the mortality is low and prognosis is excellent with early treatment.

Decousus H et al; CALISTO Study Group. Fondaparinux for the treatment of superficial-vein thrombosis in the legs. N Engl J Med. 2010 Sep 23;363(13):1222–32. [PMID: 20860504]

Decousus H et al; POST (Prospective Observational Superficial Thrombophlebitis) Study Group. Superficial venous thrombosis and venous thromboembolism: a large, prospective epidemiologic study. Ann Intern Med. 2010 Feb 16;152(4):218–24. [PMID: 20157136]

Stevens SM. ACP Journal Club: review: fondaparinux reduces VTE and recurrence in superficial thrombophlebitis of the leg. Ann Intern Med. 2012 Aug 21;157(4):JC2–4. [PMID: 22910958]

van Weert H et al. Spontaneous superficial venous thrombophlebitis: does it increase risk for thromboembolism? A historic follow-up study in primary care. J Fam Pract. 2006 Jan;55(1):52–7. [PMID: 16388768]

CHRONIC VENOUS INSUFFICIENCY

 ESSENTIALS OF DIAGNOSIS

 History of prior DVT or leg injury.

 Edema, stasis (brawny) skin pigmentation, subcutaneous liposclerosis in the lower leg.

 Large ulcerations at or above the ankle are common (stasis ulcers).

 General Considerations

Chronic venous insufficiency can result from changes secondary to acute deep venous thrombophlebitis (see Chapter 14), although a definite history of phlebitis is not obtainable in about 25% of these patients. There may be a history of leg trauma. Obesity is often a complicating factor. Chronic venous insufficiency also may occur in association with superficial venous reflux and varicose veins or as a result of neoplastic obstruction of the pelvic veins or congenital or acquired arteriovenous fistula.

The basic pathology is caused by valve leaflets that do not coapt because they are either thickened and scarred (the post-thrombotic syndrome) or in a dilated vein and are therefore functionally inadequate. This results in an abnormally high hydrostatic force transmitted to the subcutaneous veins and tissues of the lower leg. The resulting edema results in dramatic and deleterious secondary changes. The stigmata of chronic venous insufficiency include fibrosis of the subcutaneous tissue and skin, pigmentation of skin (hemosiderin taken up by the dermal macrophages) and, later, ulceration, which is extremely slow to heal. Itching may precipitate the formation of ulceration or local wound cellulitis. Dilation of the superficial veins may occur, leading to varicosities. Whereas primary varicose veins with no abnormality of the deep venous system may be associated with some similar changes, the edema is more pronounced in the post-thrombotic extremities, and the secondary changes are more extensive and debilitating.

 Clinical Findings

  1. Symptoms and Signs

Progressive pitting edema of the leg (particularly the lower leg) is the primary presenting symptom. Secondary changes in the skin and subcutaneous tissues develop over time. The usual symptoms are itching, a dull discomfort made worse by periods of standing, and pain if an ulceration is present. The skin at the ankle is usually taut from swelling, shiny, and a brownish pigmentation (hemosiderin) often develops. If the condition is long-standing, the subcutaneous tissues become thick and fibrous. Ulcerations may occur, usually just above the ankle, on the medial or anterior aspect of the leg. Healing results in a thin scar on a fibrotic base that often breaks down with minor trauma or further bouts of leg swelling. Varicosities may appear that are associated with incompetent perforating veins. Cellulitis, which is often difficult to distinguish from the hemosiderin pigmentation, may be diagnosed by blanching erythema.

  1. Imaging

Patients with post-thrombotic syndrome or signs of chronic venous insufficiency should undergo duplex ultrasonography to determine whether superficial reflux is present and to evaluate the degree of deep reflux and obstruction.

 Differential Diagnosis

Patients with heart failure, chronic kidney disease, or decompensated liver disease may have bilateral edema of the lower extremities. Swelling from lymphedema may be unilateral, but varicosities are absent. Edema from these causes pits easily and brawny discoloration is rare. Lipedema is a disorder of adipose tissue that occurs almost exclusively in women, is bilateral and symmetric, and is characterized by stopping at a distinct line just above the ankles.

Primary varicose veins may be difficult to differentiate from the secondary varicosities of chronic venous insufficiency.

Other conditions associated with chronic ulcers of the leg include neuropathic ulcers usually from diabetes mellitus, arterial insufficiency (often very painful with absent pulses), autoimmune diseases (eg, Felty syndrome), sickle cell anemia, erythema induratum (bilateral and usually on the posterior aspect of the lower part of the leg), and fungal infections.

 Prevention

Irreversible tissue changes and associated complications in the lower legs can be minimized through early and aggressive anticoagulation of acute DVT to minimize the valve damages and by prescribing compression stockings if chronic edema develops after the DVT has resolved. Catheter-directed thrombolysis or mechanical thrombectomy of acute iliofemoral DVT may be of greater value than simple anticoagulants in preventing post-thrombotic syndrome and chronic venous insufficiency.

 Treatment

  1. General Measures

Fitted, graduated compression stockings worn from the foot to just below the knee during the day and evening are the mainstays of treatment and is usually sufficient. When it is not, additional measures, such as avoidance of long periods of sitting or standing and intermittent elevations of the involved leg and sleeping with the legs kept above the level of the heart, may be necessary to control the swelling. Pneumatic compression of the leg, which can pump the fluid out of the leg, is used in cases refractory to the above measures.

  1. Ulceration

As the primary pathology is edema, healing of the ulcer will not occur until the edema is controlled. A lesion can often be treated on an ambulatory basis by means of a semi-rigid gauze boot made with Unna paste (Gelocast, Medicopaste) or a multi-layer compression (such as Profore) and applied to the leg after much of the swelling has been reduced by a period of elevation. The boot must be changed every 2–3 days, depending on the amount of drainage from the ulcer. The ulcer, tendons, and bony prominences must be adequately padded. As an alternative and after the ulcer has healed, knee-high elastic stockings with graduated compression are used in an effort to prevent recurrent edema and ulceration. If compression stockings are used with ulcers, an absorbent dressing must be applied under the stocking as the wounds can leak large volumes of fluid. The pumping action of the calf muscles on the blood flow out of the lower extremity is enhanced by a circumferential nonelastic bandage on the ankle and lower leg. Home compression therapy with a pneumatic compression device is also effective at reducing edema, but many patients have severe pain with the “milking” action of the pump device. Some patients will require admission for complete bed rest and leg elevation to achieve ulcer healing.

  1. Correction of Superficial Reflux

Compression with treatment of superficial vein reflux has been shown to decrease the recurrence rate of venous ulcers. Incompetent (refluxing) perforator veins that feed the area of ulceration can be treated with percutaneous means (radiofrequency ablation or endovenous laser treatment) to help decrease the venous pressure in the area of ulceration and promote healing. Where there is substantial obstruction of the deep venous system, superficial varicosities supply the venous return and they should not be removed.

 Prognosis

Individuals with chronic venous insufficiency often have recurrent problems, particularly if they do not consistently wear support stockings that have at least 30 mm Hg compression.

 When to Refer

  • Patients with significant saphenous reflux should be evaluated for ablation as this may reduce the recirculation of blood and return the deep system to competence.
  • Patients with ulcers should be monitored by a wound care team so that these challenging wounds can receive aggressive care.

Bergan JJ et al. Chronic venous disease. N Engl J Med. 2006 Aug 3;355(5):488–98. [PMID: 16885552]

Deatrick KB et al. Chronic venous insufficiency: current management of varicose vein disease. Am Surg. 2010 Feb;76(2):125–32. [PMID: 20336886]

Eberhard RT et al. Chronic venous insufficiency. Circulation. 2005 May 10;111(18):2398–409. [PMID: 15883226]

Gohel MS et al. Long term results of compression therapy alone versus compression plus surgery in chronic venous ulceration (ESCHAR): randomised controlled trial. BMJ. 2007 Jul 14;335(7610):83. [PMID: 17545185]

Patel NP et al. Current management of venous ulceration. Plast Reconstr Surg. 2006 Jun;117(7 Suppl):254S–260S. [PMID: 16799394]

SUPERIOR VENA CAVAL OBSTRUCTION

 ESSENTIALS OF DIAGNOSIS

 Swelling of the neck, face, and upper extremities.

 Dilated veins over the upper chest and neck.

 General Considerations

Partial or complete obstruction of the superior vena cava is a relatively rare condition that is usually secondary to neoplastic or inflammatory processes in the superior mediastinum. The most frequent causes are (1) neoplasms, such as lymphomas, primary malignant mediastinal tumors, or carcinoma of the lung with direct extension (over 80%); (2) chronic fibrotic mediastinitis, either of unknown origin or secondary to tuberculosis, histoplasmosis, pyogenic infections, or drugs, especially methysergide; (3) DVT, often by extension of the process from the axillary or subclavian vein into the innominate vein and vena cava associated with catheterization of these veins for dialysis or for hyperalimentation; (4) aneurysm of the aortic arch; and (5) constrictive pericarditis.

 Clinical Findings

  1. Symptoms and Signs

The onset of symptoms is acute or subacute. Symptoms include swelling of the neck and face, and upper extremities. Symptoms are often perceived as congestion and present as headache, dizziness, visual disturbances, stupor, syncope, or cough. Symptoms are particularly exacerbated when the patient is supine or bends over. There is progressive obstruction of the venous drainage of the head, neck, and upper extremities. The cutaneous veins of the upper chest and lower neck become dilated, and flushing of the face and neck develops. Brawny edema of the face, neck, and arms occurs later, and cyanosis of these areas then appears. Cerebral and laryngeal edema ultimately results in impaired function of the brain as well as respiratory insufficiency. Bending over or lying down accentuates the symptoms; sitting quietly is generally preferred. The manifestations are more severe if the obstruction develops rapidly and if the azygos junction or the vena cava between that vein and the heart is obstructed.

  1. Laboratory Findings

The venous pressure is elevated (often < 20 cm of water) in the arm and is normal in the leg. Since lung cancer is a common cause, bronchoscopy is often performed; transbronchial biopsy, however, is relatively contraindicated because of venous hypertension and the risk of bleeding.

  1. Imaging

Chest radiographs and a CT scan will define the location and often the nature of the obstructive process, and contrast venography or magnetic resonance venography (MRV) will map out the extent and degree of the venous obstruction and the collateral circulation. Brachial venography or radionuclide scanning following intravenous injection of technetium Tc-99m pertechnetate demonstrates a block to the flow of contrast material into the right heart and enlarged collateral veins. These techniques also allow estimation of blood flow around the occlusion as well as serial evaluation of the response to therapy.

 Treatment

Urgent treatment for neoplasm consists of (1) cautious use of intravenous diuretics and (2) mediastinal irradiation, starting within 24 hours, with a treatment plan designed to give a high daily dose but a short total course of therapy to rapidly shrink the local tumor. Intensive combined therapy will palliate the process in up to 90% of patients. In patients with a subacute presentation, radiation therapy alone usually suffices. Chemotherapy is added if lymphoma or small-cell carcinoma is diagnosed.

Conservative measures, such as elevation of the head of the bed and lifestyle modification to avoid bending over, are useful. Balloon angioplasty of the obstructed caval segment combined with stent placement provides prompt relief of symptoms and is the procedure of choice. Occasionally, anticoagulation is needed, while thrombolysis is rarely needed. Long-term outcome is complicated by risk of re-occlusion from either thrombosis or further growth of the neoplasm. Surgical procedures to bypass the obstruction are complicated by bleeding relating to high venous pressure. In cases where the thrombosis is secondary to an indwelling catheter, thrombolysis may be attempted. Clinical judgment is required since a long-standing clot may be fibrotic and the risk of bleeding will outweigh the potential benefit.

 Prognosis

The prognosis depends on the nature and degree of obstruction and its speed of onset. Slowly developing forms secondary to fibrosis may be tolerated for years. A high degree of obstruction of rapid onset secondary to cancer is often fatal in a few days or weeks because of increased intracranial pressure and cerebral hemorrhage, but treatment of the tumor with radiation and chemotherapeutic drugs may result in significant palliation. Balloon angioplasty and stenting provides good relief but may require re-treatment for recurrent symptoms secondary to thrombosis or restenosis.

 When to Refer

Referral should occur with any patient with progressive head and neck swelling to rule out superior vena cava syndrome.

 When to Admit

Any patient with acute edema of the head and neck or any patient in whom signs and symptoms of airway compromise, such as hoarseness or stridor, develop should be admitted.

Lepper PM et al. Superior vena cava syndrome in thoracic malignancies. Respir Care. 2011 May;56(5):653–66. [PMID: 21276318]

Watkinson AF et al. Endovascular stenting to treat obstruction of the superior vena cava. BMJ. 2008 Jun 21;336(7658):1434–7. [PMID: 18566082]

Wilson LD et al. Clinical practice. Superior vena cava syndrome with malignant causes. N Engl J Med. 2007 May 3;356(18):1862–9. [PMID: 17476012]

DISEASES OF THE LYMPHATIC CHANNELS

LYMPHANGITIS & LYMPHADENITIS

 ESSENTIALS OF DIAGNOSIS

 Red streak from wound or area of cellulitis toward regional lymph nodes, which are usually enlarged and tender.

 Chills, fever, and malaise may be present.

 General Considerations

Lymphangitis and lymphadenitis are common manifestations of a bacterial infection that is usually caused by hemolytic streptococci or S aureus (or by both organisms) and usually arises from the site of an infected wound. The wound may be very small or superficial, or an established abscess may be present, feeding bacteria into the lymphatics. The involvement of the lymphatics is often manifested by a red streak in the skin extending in the direction of the regional lymph nodes, which are, in turn, generally tender and engorged. Systemic manifestations include fever, chills, and malaise. The infection may progress rapidly, often in a matter of hours, and may lead to septicemia and even death.

 Clinical Findings

  1. Symptoms and Signs

Throbbing pain is usually present in the area of cellulitis at the site of bacterial invasion. Malaise, anorexia, sweating, chills, and fever of 38–40°C develop rapidly. The red streak, when present, may be definite or may be very faint and easily missed, especially in dark-skinned patients. It is usually tender or indurated in the area of cellulitis. The involved regional lymph nodes may be significantly enlarged and are usually quite tender. The pulse is often rapid.

  1. Laboratory Findings

Leukocytosis with a left shift is usually present. Blood cultures may be positive, most often for staphylococcal or streptococcal species. Culture and sensitivity studies of the wound exudate or pus may be helpful in treatment of the more severe or refractory infections but are often difficult to interpret because of skin contaminants.

 Differential Diagnosis

Lymphangitis may be confused with superficial thrombophlebitis, but the erythema and induration of thrombophlebitis is localized in and around the thrombosed vein. Venous thrombosis is not associated with lymphadenitis, and a wound of entrance with secondary cellulitis is generally absent.

Cat-scratch fever (Bartonella henselae) should be considered when lymphadenitis is present; the nodes, though often very large, are relatively nontender. Exposure to cats is common, but the patient may have forgotten about the scratch.

It is extremely important to differentiate cellulitis from acute streptococcal hemolytic gangrene or necrotizing fasciitis. These are deeper infections that may be extensive and are potentially lethal. Patients appear more seriously ill; there may be redness due to leakage of red cells, creating a non-blanching erythema; and subcutaneous crepitus may be palpated or auscultated using the diaphragm with light pressure over the involved area. Immediate wide debridement of all involved deep tissues should be done if these signs are present.

 Treatment

  1. General Measures

Prompt treatment should include heat (hot, moist compresses or heating pad), elevation when feasible, and immobilization of the infected area. Analgesics may be prescribed for pain.

  1. Specific Measures

Empiric antibiotic therapy for hemolytic streptococci or S aureus (or by both organisms) should always be instituted when local infection becomes invasive, as manifested by cellulitis and lymphangitis. Because such infections are so frequently caused by streptococci, cephalosporins or extended-spectrum penicillins are commonly used (eg, cephalexin, 0.5 g orally four times daily for 7–10 days; see Table 30–6). Given the increasing incidence of methicillin-resistant S aureus (MRSA) in the community, coverage of this pathogen with appropriate antibiotic therapy (eg, trimethoprim-sulfamethoxazole, two double strength tablets twice daily for 7–10 days) should be considered (see Tables 30–4 and 30–6).

  1. Wound Care

Any wound that is the initiating site of lymphangitis should be treated aggressively. Any necrotic tissue must be debrided and loculated pus drained.

 Prognosis

With proper therapy including an antibiotic effective against the invading bacteria, control of the infection can usually be achieved in a few days. Delayed or inadequate therapy can lead to overwhelming infection with septicemia.

 When to Admit

Infections causing lymphangitis should be treated in the hospital with intravenous antibiotics. Debridement may be required.

LYMPHEDEMA

 ESSENTIALS OF DIAGNOSIS

 Painless persistent edema of one or both lower extremities, primarily in young women.

 Pitting edema without ulceration, varicosities, or stasis pigmentation.

 There may be episodes of lymphangitis and cellulitis.

 General Considerations

When lymphedema is due to congenital developmental abnormalities consisting of hypoplastic or hyperplastic involvement of the proximal or distal lymphatics, it is referred to as the primary form. The obstruction may be in the pelvic or lumbar lymph channels and nodes when the disease is extensive and progressive. The secondary form of lymphedema involves inflammatory or mechanical lymphatic obstruction from trauma, regional lymph node resection or irradiation, or extensive involvement of regional nodes by malignant disease or filariasis. Lymphedema may occur following surgical removal of the lymph nodes in the groin or axillae. Secondary dilation of the lymphatics that occurs in both forms leads to incompetence of the valve system, disrupts the orderly flow along the lymph vessels, and results in progressive stasis of a protein-rich fluid. Episodes of acute and chronic inflammation may be superimposed, with further stasis and secondary fibrosis.

 Clinical Findings

Hypertrophy of the limb results, with markedly thickened and fibrotic skin and subcutaneous tissue in very advanced cases.

Lymphangiography and radioactive isotope studies may identify focal defects in lymph flow but are of little value in planning therapy. T2–weighted MRI has been used to identify lymphatics and proximal obstructing masses.

 Treatment

Since there is no effective cure for lymphedema, the treatment strategies are designed to control the problem and allow normal activity and function. Most patients can be treated with some of the following measures: (1) The flow of lymph out of the extremity can be aided through intermittent elevation of the extremity, especially during the sleeping hours (foot of bed elevated 15–20 degrees, achieved by placing pillows beneath the mattress); the constant use of graduated elastic compression stockings; and massage toward the trunk—either by hand or by means of pneumatic pressure devices designed to milk edema out of an extremity. (2) Secondary cellulitis in the extremity should be avoided by means of good hygiene and treatment of any trichophytosis of the toes. Once an infection starts, it should be treated by periods of elevation and antibiotic therapy that covers Staphylococcus and Streptococcus organisms (see Table 30–6). Infections can be a serious and recurring problem and are often difficult to control. Prophylactic antibiotics have not been shown to be of benefit. (3) Intermittent courses of diuretic therapy, especially in those with premenstrual or seasonal exacerbations, are rarely helpful. (4) Amputation is used only for the rare complication of lymphangiosarcoma in the extremity.

 Prognosis

With aggressive treatment, including pneumatic compression devices, good relief of symptoms can be achieved. The long-term outlook is dictated by the associated conditions and avoidance of recurrent cellulitis.

Ashikaga T et al; National Surgical Adjuvant Breast, Bowel Project. Morbidity results from the NSABP B-32 trial comparing sentinel lymph node dissection versus axillary dissection. J Surg Oncol. 2010 Aug 1;102(2):111–8. [PMID: 20648579]

Haghighat S et al. Comparing two treatment methods for post mastectomy lymphedema: complex decongestive therapy alone and in combination with intermittent pneumatic compression. Lymphology. 2010 Mar;43(1):25–33. [PMID: 20552817]

Murdaca G et al. Current views on diagnostic approach and treatment of lymphedema. Am J Med. 2012 Feb;125(2):134–40. [PMID: 22269614]

Rockson SG. Diagnosis and management of lymphatic vascular disease. J Am Coll Cardiol. 2008 Sep 2;52(10):799–806. [PMID: 18755341]

Torres Lacomba M et al. Effectiveness of early physiotherapy to prevent lymphoedema after surgery for breast cancer: randomised, single blinded, clinical trial. BMJ. 2010 Jan 12;340:b5396. [PMID: 20068255]

SHOCK

 ESSENTIALS OF DIAGNOSIS

 Hypotension, tachycardia, oliguria, altered mental status.

 Peripheral hypoperfusion and impaired oxygen delivery.

 General Considerations

Shock occurs when the rate of arterial blood flow is inadequate to meet tissue metabolic needs. This results in regional hypoxia and subsequent lactic acidosis from anaerobic metabolism in peripheral tissues as well as eventual end-organ damage and failure.

 Classification (Table 12–1)

Table 12–1. Classification of shock by mechanism and common causes.

  1. Hypovolemic Shock

Hypovolemic shock results from decreased intravascular volume secondary to loss of blood or fluids and electrolytes. The etiology may be suggested by the clinical setting (eg, trauma) or by signs and symptoms of blood loss (eg, gastrointestinal bleeding) or dehydration (eg, vomiting or diarrhea). Compensatory vasoconstriction may transiently maintain the blood pressure but unreplaced losses of over 15% of the intravascular volume can result in hypotension and progressive tissue hypoxia.

  1. Cardiogenic Shock

Cardiogenic shock results from cardiac failure with the resultant inability of the heart to maintain adequate tissue perfusion. The clinical definition of cardiogenic shock is evidence of tissue hypoxia due to decreased cardiac output (cardiac index < 2.2 L/min/m2) in the presence of adequate intravascular volume. This is most often caused by myocardial infarction but can also be due to cardiomyopathy, myocardial contusion, valvular incompetence or stenosis, or arrhythmias. See Chapter 10.

  1. Obstructive Shock

Cardiac tamponade, tension pneumothorax, and massive pulmonary embolism can cause an acute decrease in cardiac output resulting in shock. These are medical emergencies requiring prompt diagnosis and treatment.

  1. Distributive Shock

Distributive or vasodilatory shock has many causes including sepsis, anaphylaxis, systemic inflammatory response syndrome (SIRS) produced by severe pancreatitis or burns, traumatic spinal cord injury, or acute adrenal insufficiency. The reduction in systemic vascular resistance results in inadequate cardiac output and tissue hypoperfusion despite normal circulatory volume.

  1. Septic shock—Sepsis is the most common cause of distributive shock and carries a mortality rate of 20–50%. Sepsis is defined as the presence of infection (either documented or suspected) in conjunction with systemic manifestations of infection. Septic shock is diagnosed whenhypotension from sepsis persists despite adequate fluid resuscitation. The most common cause of septic shock in hospitalized patients is infection with gram-positive or gram-negative organisms; polymicrobial infections are almost as likely. The incidence of sepsis from fungal organisms is increasing but remains less than that for bacterial infections. Risk factors for septic shock include bacteremia, extremes of age, diabetes, cancer, immunosuppression, and history of a recent invasive procedure.
  2. Systemic inflammatory response syndrome (SIRS)—Defined as a systemic response to a nonspecific infectious or noninfectious insult—such as from burns, pancreatitis, an autoimmune disorder, ischemia, or trauma—the presence of two or more of the following clinical criteria help establish the diagnosis of SIRS: (1) body temperature> 38oC (100.4oF) or < 36oC (96.8oF), (2) heart rate > 90 beats per minute, (3) respiratory rate more than 20 breaths per minute or hyperventilation with an arterial carbon dioxide tension (Paco2) > 32 mm Hg, (4) abnormal white blood cell count (> 12,000/mcL or < 4000/mcL or > 10% immature (band) forms). When a source of infection is confirmed, SIRS is categorized as sepsis.
  3. Neurogenic shock—Neurogenic shock is caused by traumatic spinal cord injury or effects of an epidural or spinal anesthetic. This results in loss of sympathetic tone with a reduction in systemic vascular resistance and hypotension without a compensatory tachycardia. Reflex vagal parasympathetic stimulation evoked by pain, gastric dilation, or fright may simulate neurogenic shock, producing hypotension, bradycardia, and syncope.

 Clinical Findings

  1. Symptoms and Signs

Hypotension is traditionally defined as a systolic blood pressure of ≤ 90 mm Hg or a mean arterial pressure of < 60–65 mm Hg but must be evaluated relative to the patient’s normal blood pressure. A drop in systolic pressure of > 10–20 mm Hg or an increase in pulse of > 15 beats per minute with positional change suggests depleted intravascular volume. However, blood pressure is often not the best indicator of end-organ perfusion because compensatory mechanisms, such as increased heart rate, increased cardiac contractility, and vasoconstriction can occur to prevent hypotension. Patients with hypotension often have cool or mottled extremities and weak or thready peripheral pulses. Splanchnic vasoconstriction may lead to oliguria, bowel ischemia, and hepatic dysfunction, which can ultimately result in multi-organ failure. Mentation may be normal or patients may become restless, agitated, confused, lethargic, or comatose as a result of inadequate perfusion of the brain.

Hypovolemic shock is evident when signs of hypoperfusion, such as oliguria, altered mental status, and cool extremities, are present. Jugular venous pressure is low, and there is a narrow pulse pressure indicative of reduced stroke volume. Rapid replacement of fluids restores tissue perfusion. In cardiogenic shock, there are also signs of global hypoperfusion with oliguria, altered mental status, and cool extremities. Jugular venous pressure is elevated and there may be evidence of pulmonary edema with respiratory compromise in the setting of left-sided heart failure. A transthoracic echocardiogram (TTE) or a transesophageal echocardiogram (TEE) is an effective diagnostic tool to differentiate hypovolemic from cardiogenic shock. In hypovolemic shock, the left ventricle will be small because of decreased filling, but contractility is often preserved. Cardiogenic shock results from cardiac failure with a resultant decrease in left ventricular contractility. In some cases, the left ventricle may appear dilated and full because of the inability of the left ventricle to eject a sufficient stroke volume.

In obstructive shock, the central venous pressure may be elevated but the TTE or TEE may show reduced left ventricular filling, a pericardial effusion in the case of tamponade, or thickened pericardium as in the case of pericarditis. Pericardiocentesis or pericardial window for pericardial tamponade, chest tube placement for tension pneumothorax, or catheter-directed thrombolytic therapy in the case of massive pulmonary embolism can be life-saving in cases of obstructive shock.

In distributive shock, signs include hyperdynamic heart sounds, warm extremities initially, and a wide pulse pressure indicative of large stroke volume. The echocardiogram may show a hyperdynamic left ventricle. Fluid resuscitation may have little effect on blood pressure, urinary output, or mentation. Septic shock is diagnosed when there is clinical evidence of infection in the setting of persistent hypotension and evidence of organ hypoperfusion, such as lactic acidosis, decreased urinary output, or altered mental status despite adequate volume resuscitation. Neurogenic shock is diagnosed when there is evidence of central nervous system injury and persistent hypotension despite adequate volume resuscitation.

  1. Laboratory Findings and Imaging

Blood specimens should be evaluated for complete blood count, electrolytes, glucose, arterial blood gas determinations, coagulation parameters, lactate levels, typing and cross-matching, and bacterial cultures. An electrocardiogram and chest radiograph should also be part of the initial assessment.

 Treatment

  1. General Measures

Treatment depends on prompt diagnosis and an accurate appraisal of inciting conditions. Initial management consists of basic life support with an assessment of the patient’s airway, breathing, and circulation. This may entail airway intubation and mechanical ventilation. Ventilatory failure should be anticipated in patients with a severe metabolic acidosis in association with shock. Mechanical ventilation along with sedation can decrease the oxygen demand of the respiratory muscles and allow improved oxygen delivery to other hypoperfused tissues. Intravenous access and fluid resuscitation should be instituted along with cardiac monitoring and assessment of hemodynamic parameters such as blood pressure and heart rate. Cardiac monitoring can detect myocardial ischemia or malignant arrhythmias, which can be treated by standard advanced cardiac life support (ACLS) protocols.

Unresponsive or minimally responsive patients should have their glucose checked immediately and if their glucose level is low, 1 ampule of 50% dextrose intravenously should be given. An arterial line should be placed for continuous blood pressure measurement, and a Foley catheter should be inserted to monitor urinary output.

  1. Central Venous Pressure

Early consideration is given to placement of a central venous catheter (CVC) for infusion of fluids and medications and for hemodynamic pressure measurements. A CVC can provide measurements of the central venous pressure (CVP) and the central venous oxygen saturation (ScvO2), both of which can be used to manage sepsis and septic shock. Pulmonary artery catheters (PACs) allow measurement of the pulmonary artery pressure, left-sided filling pressure or the pulmonary capillary wedge pressure (PCWP), the mixed venous oxygen saturation (SvO2) and cardiac output. Meta-analyses of multiple studies, including randomized controlled trials, suggest that the use of PACs do not increase overall mortality or length of hospital stay, but are associated with higher use of inotropes and intravenous vasodilators in critically ill patients from different patient populations (including those with sepsis, myocardial ischemia, and those who were postsurgical). Thus, the routine use of PACs cannot be recommended. However, in some complex situations, PACs may be useful in distinguishing between cardiogenic and septic shock. The attendant risks associated with PACs (such as infection, arrhythmias, vein thrombosis, and pulmonary artery rupture) can be as high as 4–9%; therefore, the value of the information they might provide must be carefully weighed in each patient. TTE is a noninvasive alternative to the PAC. TTE can provide information about the pulmonary artery pressure, PCWP, and cardiac output; in addition, TTE can provide valuable information about current cardiac function. The SvO2, one parameter used to guide sepsis management, is obtained through the PAC. However, the ScvO2, which is obtained through the CVC, is similar to the SvO2 and can be used as a surrogate. Pulse pressure variation, as determined by arterial waveform analysis, or stroke volume variation are much more sensitive than CVP as a measure of fluid responsiveness in volume resuscitation, but these measurements are only valid in patients who are mechanically ventilated and in normal sinus rhythm.

A CVP < 5 mm Hg suggests hypovolemia, and a CVP over 18 mm Hg suggests volume overload, cardiac failure, tamponade, or pulmonary hypertension. A cardiac index < 2 L/min/m2 indicates a need for inotropic support. A high cardiac index > 4 L/min/m2 in a hypotensive patient is consistent with early septic shock. The systemic vascular resistance is low (< 800 dynes. s/cm–5) in sepsis and neurogenic shock and high (> 1500 dynes. s/cm–5) in hypovolemic and cardiogenic shock. Treatment is directed at maintaining a CVP of 8–12 mm Hg, a mean arterial pressure of 65–90 mm Hg, a cardiac index of 2–4 L/min/m2, and a ScvO2 < 70%.

  1. Volume Replacement

Volume replacement is critical in the initial management of shock. Hemorrhagic shock is treated with immediate efforts to achieve hemostasis and rapid infusions of blood substitutes, such as type-specific or type O negative packed red blood cells (PRBCs) or whole blood, which also provides extra volume and clotting factors. Each unit of PRBC or whole blood is expected to raise the hematocrit by 3%.Hypovolemic shock secondary to dehydration is managed with rapid boluses of isotonic crystalloid (0.9% saline or lactated Ringer solution) usually in 1-liter increments. Cardiogenic shock in the absence of fluid overload requires smaller fluid challenges, usually in increments of 250 mL. Septic shock usually requires large volumes of fluid for resuscitation (usually < 2 L) as the associated capillary leak releases fluid into the extravascular space. Caution must be used with large-volume resuscitation with unwarmed fluids because this can produce hypothermia, which can lead to hypothermia-induced coagulopathy. Warming of fluids before administration can avoid this complication.

Meta-analyses of studies of heterogenous critically ill populations comparing crystalloid and colloid resuscitation (with albumin) indicate no benefit of colloid over crystalloid solutions except in trauma patients with traumatic brain injury who had a higher mortality if albumin was used for volume resuscitation. Clinical trials and meta-analyses have also found no difference in mortality between trauma patients receiving hypertonic saline (7.5%) and those receiving isotonic crystalloid. More positive results were found with hypertonic saline plus dextran with an increase in survival over patients managed with isotonic saline, particularly in patients with traumatic brain injury.

  1. Early Goal-Directed Therapy

Early goal-directed therapy following set protocols for the treatment of septic shock provides significant benefits (see www.survivingsepsis.org). In a 2001 randomized controlled trial, patients with severe sepsis or septic shock were assigned to receive either 6 hours of early goal-directed therapy or usual care prior to admission to the intensive care unit. Patients assigned to early goal-directed care received fluid resuscitation to achieve a CVP of 8–12 mm Hg; vasopressors to maintain a mean arterial blood pressure of at least 65 mm Hg; PRBCs to reach a hematocrit of 30% if the ScvO2 was < 70%; and if, after PRBC transfusion, the ScvO2 remained < 70%, dobutamine to raise the ScvO2 > 70%. When compared with controls, these patients had a significantly lower in-hospital mortality rate (46.5% for standard therapy, 30.5% for early goal-directed therapy; P =.009) and 60-day mortality rate (57% for standard therapy, 44% for early goal-directed therapy; P =.03). A meta-analysis of hemodynamic optimization trials has also suggested that early treatment before the development of organ failure results in improved survival. Lactate clearance of > 10% can be used as a potential substitute for ScvO2criteria if ScvO2 monitoring is not available.

Compensated shock can occur in the setting of normalized hemodynamic parameters with ongoing global tissue hypoxia. Traditional endpoints of resuscitation such as blood pressure, heart rate, urinary output, mental status, and skin perfusion can therefore be misleading. Additional endpoints such as lactate levels and base deficit can help guide further resuscitative therapy. Patients who respond well to initial efforts demonstrate a survival advantage over nonresponders.

  1. Medications
  2. Vasoactive therapy—Vasopressors and inotropic agents are administered only after adequate fluid resuscitation. Choice of vasoactive therapy depends on the presumed etiology of shock as well as cardiac output. If there is continued hypotension with evidence of high cardiac output after adequate volume resuscitation, then vasopressor support is needed to improve vasomotor tone. If there is evidence of low cardiac output with high filling pressures, inotropic support is needed to improve contractility.

For vasodilatory shock when increased vasoconstriction is required to maintain an adequate perfusion pressure, alpha-adrenergic agonists (such as norepinephrine and phenylephrine) are generally used. Although norepinephrine is both an alpha-adrenergic and beta-adrenergic agonist, it preferentially increases mean arterial pressure over cardiac output. The initial dose is 1–2 mcg/min as an intravenous infusion, titrated to maintain the mean arterial blood pressure to at least 65 mm Hg. The usual maintenance dose is 2–4 mcg/min intravenously (maximum dose is 30 mcg/min). Patients with refractory shock may require dosages of 10–30 mcg/min intravenously. Epinephrine, also with both alpha-adrenergic and beta-adrenergic effects, may be used in severe shock and during acute resuscitation. It is the vasopressor of choice for anaphylactic shock. For severe shock, give 1 mcg/min as a continuous intravenous infusion initially and titrate to hemodynamic response; the usual dosage range is 1–10 mcg/min intravenously.

Dopamine has variable effects according to dosage. At low doses (2–5 mcg/kg/min intravenously), stimulation of dopaminergic and beta-adrenergic receptors produces increased glomerular filtration, heart rate, and contractility. At doses of 5–10 mcg/kg/min, beta-1-adrenergic effects predominate, resulting in an increase in heart rate and cardiac contractility. At higher doses (> 10 mcg/kg/min), alpha-adrenergic effects predominate, resulting in peripheral vasoconstriction. The maximum dose is typically 50 mcg/kg/min.

There is no evidence documenting a survival benefit from, or the superiority of, a particular vasopressor in septic shock. Norepinephrine is the initial vasopressor of choice in septic shock to maintain the mean arterial pressure > 65 mm Hg. Phenylephrine can be used as a first-line agent for hyperdynamic septic shock if (1) there is low systemic venous resistance but high cardiac output, which can manifest as hypotension with warm extremities or (2) dysrhythmias or tachycardias prevent the use of agents with beta-adrenergic activity. The use of dopamine as a first-line vasopressor in septic shock was shown in a meta-analysis to increase 28-day mortality and to have a higher incidence of arrhythmic events. Dopamine should only be used as an alternative to norepinephrine in select patients with septic shock, including patients with significant bradycardia or low potential for tachyarrhythmias.

Vasopressin (antidiuretic hormone or ADH) is often used as an adjunctive therapy to catecholamine vasopressors in the treatment of distributive or vasodilatory shock. Vasopressin causes peripheral vasoconstriction via V1 receptors located on smooth muscle cells and attenuation of nitric oxide (NO) synthesis and cGMP, the second messenger of NO. The rationale for using low-dose vasopressin in the management of septic shock includes the relative deficiency of vasopressin in late shock and the increased sensitivity of the systemic circulation to the vasopressor effects of vasopressin. Vasopressin also potentiates the effects of catecholamines on the vasculature and stimulates cortisol production. In the Vasopressin and Septic Shock Trial (VASST), low doses of vasopressin did not reduce mortality compared with norepinephrine in patients with septic shock who were being treated with catecholamine vasopressors. Some studies have reported reduced catecholamine requirements with vasopressin administration. Intravenous infusion of vasopressin at a low dose (0.01–0.04 units/min) may be safe and beneficial in septic patients with hypotension that is refractory to fluid resuscitation and conventional catecholamine vasopressors. Higher doses of vasopressin decrease cardiac output and may put patients at greater risk for splanchnic and coronary artery ischemia. Studies do not favor the use of vasopressin as first-line therapy, but it may be as a second-line agent in refractory septic or anaphylactic shock; its role as an initial vasopressor warrants further study.

There is insufficient evidence to recommend a specific vasopressor for use in cardiogenic shock, but expert opinion suggests that either norepinephrine or dopamine should be used as a first-line agent. Dobutamine, a predominantly beta-adrenergic agonist, increases contractility and decreases afterload. It is used for patients with low cardiac output and high PCWP but who do not have hypotension. Dobutamine can be added to a vasopressor if there is reduced myocardial function (decreased cardiac output and elevated PCWP), or if there are signs of hypoperfusion despite adequate volume resuscitation and an adequate mean arterial pressure. The initial dose is 0.1–0.5 mcg/kg/min as a continuous intravenous infusion, which can be titrated every few minutes as needed to achieve a hemodynamic effect; the usual dosage range is 2–20 mcg/kg/min intravenously. Tachyphylaxis can occur after 48 hours from the down-regulation of beta-adrenergic receptors. Amrinone or milrinone are phosphodiesterase inhibitors that can be substituted for dobutamine. These drugs increase cyclic AMP levels and increase cardiac contractility, bypassing the beta-adrenergic receptor. Vasodilation is a side effect of both amrinone and milrinone.

  1. Corticosteroids—Corticosteroids are the treatment of choice in patients with shock secondary to adrenal insufficiency but studies do not support their use in patients with shock from sepsis or other etiologies. The observation that severe sepsis may be associated with relative adrenal insufficiency or glucocorticoid receptor resistance has led to several trials to evaluate the role of treatmentwith corticosteroids in septic shock. Early trials where high doses of corticosteroids were administered to patients in septic shock did not show improved survival; rather, some worse outcomes were observed from increased rates of secondary infections. Investigators have studied the use of low-dose corticosteroids in patients who were in septic shock and had relative adrenal insufficiency, defined by a cortisol response of 9 mcg/dL or less after one injection of 250 mcg of corticotropin. In 2008, the Corticosteroid Therapy of Septic Shock (CORTICUS) study demonstrated that low-dose hydrocortisone (50 mg intravenously every 6 hours for 5 days and then tapered over 6 days) did not improve survival in patients with septic shock, either overall or in patients who had relative adrenal insufficiency. This study was a randomized, double-blinded, placebo-controlled trial that is the largest to date of corticosteroids in septic patients. One limitation of the CORTICUS trial was that it was not adequately powered to detect a clinically important difference in mortality. Meta-analyses of multiple smaller trials of corticosteroids in patients with septic shock demonstrated that when shock was poorly responsive to fluid resuscitation and vasopressors, low-dose hydrocortisone (300 mg/d or less in divided doses) increased the mean arterial pressure but did not show a mortality benefit.
  2. Antibiotics—Definitive therapy for septic shock includes an early initiation of empiric broad-spectrum antibiotics after appropriate cultures have been obtained. Imaging studies may prove useful to attempt localization of sources of infection. Surgical management may also be necessary if necrotic tissue or loculated infections are present (seeTable 30–5).
  3. Sodium bicarbonate—For patients with sepsis of any etiology and lactic acidosis, clinical studies have failed to show any hemodynamic benefit from bicarbonate therapy, either in increasing cardiac output or in decreasing the vasopressor requirement even in patients with severe acidemia.
  4. Other Treatment Modalities

Cardiac failure may require use of transcutaneous or transvenous pacing or placement of an intra-arterial balloon pump. Emergent revascularization by percutaneous angioplasty or coronary artery bypass surgery appears to improve long-term outcome with increased survival compared with initial medical stabilization for patients with myocardial ischemia leading to cardiogenic shock. Urgent hemodialysis or continuous venovenous hemofiltration may be indicated for maintenance of fluid and electrolyte balance during acute kidney injury resulting in shock from multiple modalities.

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