Current Medical Diagnosis and Treatment 2007 (Current Medical Diagnosis & Treatment) - page 18

Editors: McPhee, Stephen J.; Papadakis, Maxine A.; Tierney, Lawrence M.

Title: Current Medical Diagnosis & Treatment, 46th Edition

Copyright ©2007 McGraw-Hill

> Table of Contents > 12 - Blood Vessels & Lymphatics

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12

Blood Vessels & Lymphatics

Louis M. Messina MD

Most arterial occlusive disease is produced by atherosclerosis. Atherosclerosis is a generalized response of the artery wall to injury. Atherosclerotic plaques are characterized by smooth muscle migration into the intima and subsequent proliferation and extracellular lipid deposition. Complex lesions are composed of a fibrous cap containing smooth muscle and inflammatory cells overlying a central core of lipid-rich necrotic debris. Clinical symptoms are produced by progressive stenosis, calcification, intraplaque hemorrhage, distal embolization, and luminal thrombosis after cap rupture. Atherosclerosis is a systemic disease, associated with some degree of involvement of all major arteries, but its most common clinical manifestations involve a limited number of arteries at areas of turbulent flow and low sheer stress: the carotid bifurcation, the infrarenal aorta and the iliac, superficial femoral, and tibial arteries, and the ostia of the renal and visceral arteries.

Most arterial aneurysms are classified as atherosclerotic or degenerative, because atheromas are found in the aneurysm wall and many patients have typical atherosclerotic risk factors. Both occlusive disease and aneurysms may be present in the same individual. However, the exact role of atherosclerosis in the causation of aneurysms is poorly defined. An imbalance of tissue metalloproteinases and metalloproteinase inhibitors is responsible for elastin and collagen degradation. Genetic predisposition, inflammation, and hemodynamic factors may also play a permissive role in aneurysm formation.

Atherosclerosis has been associated with increasing age, hypercholesterolemia, diabetes mellitus, smoking, a positive family history, hypertension, elevated levels of lipoprotein(a) and C-reactive protein, sedentary lifestyle, obesity, and homocystinuria. Control of risk factors by use of antihypertensive and lipid-lowering medications, regulation of blood sugar, tobacco cessation, and regular exercise remain the mainstays of treatment. Aspirin and clopidogrel (and potentially glycoprotein IIb/IIIa inhibitors) may prevent microemboli by impairing platelet aggregation; clopidogrel reduces the relative risk of stroke, myocardial infarction, and vascular death by 24% over aspirin alone in at-risk patients. Preliminary studies suggest that antioxidants, particularly dietary vitamin E, may also be beneficial in slowing the progression of disease.

Bhatt DL et al; REACH Registry Investigators: International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA 2006; 295:180.

Chapman MJ: Beyond the statins: new therapeutic perspectives in cardiovascular disease prevention. Cardiovasc Drugs Ther 2005;19:135.

Arterial Aneurysms

Aneurysms of the Abdominal Aorta

Essentials of Diagnosis

  • Most aortic aneurysms are asymptomatic, detected during a routine physical examination or a diagnostic study.

  • Severe back or abdominal pain, a pulsatile mass, and hypotension indicate rupture.

  • Concomitant atherosclerotic occlusive disease of the lower extremities is present in 25% of patients.

General Considerations

Over 90% of abdominal aneurysms originate below the renal arteries, and many extend into the common iliac arteries. The infrarenal aorta is normally 2 cm in diameter; an aneurysm is defined by an aortic diameter that exceeds 3 cm. An aortic aneurysm is present in 5–8% of men over the age of 65 years. The reported incidence has tripled over the past 30 years. Routine ultrasound screening of high-risk groups is associated with a 53% reduction in aneurysm-related deaths. Half of all newly detected aneurysms are under 5 cm in diameter, and nearly two-thirds of these will increase sufficiently in size to require repair. β-Blockers and, more recently, oral roxithromycin (300 mg daily for 30 days) have been shown to decrease the expansion rate of small aneurysms. Patients with chronic obstructive

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pulmonary disease appear more likely to rupture smaller aneurysms.

Clinical Findings

A. Symptoms and Signs

1. Asymptomatic aneurysms

An aneurysm may be suspected on routine physical examination by detection of a prominent aortic pulsation. More often, asymptomatic aneurysms are discovered as incidental findings on abdominal ultrasound or CT scan. Peripheral pulses are often normal, but coexisting renal or lower extremity arterial occlusive disease is present in 25% of patients. Popliteal artery aneurysms are present in 15% of patients with aneurysms of the abdominal aorta, and, conversely, more than one-third of patients with popliteal aneurysms have abdominal aortic aneurysms.

2. Symptomatic aneurysms

Midabdominal or lower back pain (or both) in the presence of a prominent aortic pulsation may indicate rapid aneurysmal growth, rupture, or an inflammatory aortic aneurysm. Inflammatory aneurysms account for fewer than 5% of aortic aneurysms and are characterized by extensive periaortic and retroperitoneal inflammation of unknown cause. These patients may have low-grade fever, elevated sedimentation rate, and a history of recent upper respiratory tract infection; they are often active smokers. Infected aortic aneurysms (either caused by septic emboli to a normal aorta or bacterial colonization of an existing aneurysm) are rare but should be suspected in patients with saccular aneurysms or aneurysms in conjunction with fever of unknown origin, particularly if blood cultures are positive for Salmonella. Peripheral emboli can also be a symptom of aneurysmal disease.

3. Ruptured aneurysms

Patients with ruptured aortic aneurysms present with severe back, abdominal, or flank pain and hypotension. Posterior rupture confined to the retroperitoneum carries a better prognosis than anterior rupture into the peritoneal cavity. As many as 90% of patients die either before they reach the hospital or in the immediate perioperative period. The only chance for survival is emergent surgical repair.

B. Laboratory Findings

ECG, serum creatinine, hematocrit and hemoglobin, and type and cross-match should be obtained routinely in all patients.

C. Imaging

Abdominal ultrasonography is the screening study of choice and is valuable also for following aneurysm growth in patients with small (< 5 cm) aneurysms. Aneurysms typically grow by about 10% of their diameter per year; annual ultrasound examinations are recommended for aneurysms greater than 3.5 cm. In about 75% of patients, size can be estimated by measurement of curvilinear calcifications in the aneurysm wall on an abdominal radiograph, but this is much less accurate than ultrasonography.

Contrast-enhanced CT scanning not only precisely sizes the aneurysm but also defines its relationship to the renal arteries. MRI is as sensitive and specific as CT and is useful if renal insufficiency precludes contrast-enhanced CT. Aortography is indicated prior to elective aneurysm repair when arterial occlusive disease of the visceral or lower extremity arteries is suspected or when endograft repair is being considered.

Treatment

A. Standard Therapy

Unless contraindicated, all patients should receive perioperative β-blockade to reduce cardiac complications. Surgical excision and synthetic graft replacement are the treatment of choice for most aneurysms of the infrarenal abdominal aorta that are greater than 5 cm. The maximum diameter of the aneurysm correlates best with the risk of rupture. Yearly rupture risk is 2% for 4- to 5.5-cm aneurysms, 7% for 6- to 6.9-cm aneurysms, and 25% for 7-cm aneurysms. Recommendation of an elective repair must be balanced with the risk of rupture. In asymptomatic good-risk patients, surgery is advised when the aneurysm exceeds 5 cm, whereas poor-risk patients may not be considered for repair until the aneurysm exceeds 6 cm. Urgent repair is indicated for symptomatic patients irrespective of aneurysm size.

Preoperative evaluation must include a detailed assessment of cardiac risk and examination of the carotid arteries since acute myocardial infarction, arrhythmia, and stroke remain the most frequent perioperative complications. In patients with asymptomatic aneurysms and a history of angina or of carotid stenosis greater than 80%, coronary angioplasty, coronary bypass grafting, or carotid endarterectomy may be indicated before repair of the aneurysm.

B. Endovascular Repair

Endovascular stent grafts, or “covered stents,” have evolved over the past decade for treatment of aortic aneurysms. Aortic stent grafts are configured to be uni-iliac or bifurcated depending on the particular anatomy of the aneurysm. Uni-iliac grafts are combined with endovascular occlusion of the contralateral common iliac artery and femoral-femoral bypass grafting. Both types of grafts are deployed via the common femoral arteries; in most cases, this involves bilateral inguinal incisions. The operation can be performed under epidural anesthesia, often in less than 2 hours and with minimal blood loss, which has made repair of aortic aneurysms feasible in high-risk patients previously deemed inoperable. Additional advantages include reduced incisional pain, fewer cardiopulmonary complications, and avoidance

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of postoperative ileus; most patients are discharged from the hospital on the second postoperative day. Endografts have been used successfully for repair of ruptured aneurysms, using balloon catheter control of the supraceliac aorta to facilitate intraoperative angiography and stent deployment.

Not all patients are candidates for standard endovascular repair. The proximal neck of the aneurysm must be adequate (at least 1.5 cm in length and less than 3 cm in width) to allow fixation and sufficient tissue apposition below the renal arteries. Iliac artery aneurysms, iliac stenoses, and iliac tortuosity or calcification all increase the complexity of stent deployment. The newest technology includes use of smaller introducer sheaths for percutaneous deployment. Long-term durability of endovascular grafts needs to be established before comparison can be made with open repair for use in the good-risk patient with asymptomatic aortic aneurysm. Objective comparison with open surgical repair has been complicated by the multiplicity of continually evolving stent graft designs.

Complications

Complications after aneurysm resection include myocardial infarction, bleeding, respiratory insufficiency, ischemic colitis, limb ischemia, renal insufficiency, and stroke. Bowel infarction, liver dysfunction, acalculous cholecystitis, and renal failure are more common with emergent aneurysm repair or when repair of the aneurysm requires supraceliac or suprarenal cross-clamping. However, renal insufficiency can occur even when the clamp is infrarenal and there is no reported intraoperative hypotension, presumably because of renal artery vasoconstriction, atheroemboli, preoperative contrast administration for CT scan, and dehydration from fasting or bowel preparation. For this reason, mannitol (25-g intravenous bolus) is given as a diuretic and free-radical scavenger prior to cross-clamping, and dopamine (3 mcg/kg/min) or fenoldopam (0.05–0.1 mcg/kg/min) is continued in the immediate postoperative period to increase renal perfusion and glomerular filtration rate. Rarely (0.1% of cases), lower extremity paralysis complicates repair of abdominal aortic aneurysm because of occlusion of the spinal artery from atheroemboli, shock, or aortic cross-clamping. Graft infection and graft-enteric fistulas are late complications, occurring more often after emergent aneurysm repair. One complication specific to endovascular repair is persistent filling of the aneurysm (endoleak). Endoleaks are classified as type 1 (leak around the top or bottom of the stent graft), type 2 (leak from a back-bleeding patent lumbar artery or inferior mesenteric artery), and type 3 (leak through the graft material). They are detected by contrast CT obtained routinely on postoperative day 30, and at 6-month or yearly intervals thereafter. Type 1 endoleaks are restented to allow adequate proximal or distal fixation. Type 2 endoleaks are not uncommon (20–30% of patients) in the immediate postoperative period but usually disappear by the 1-month CT scan. Persistent type 2 endoleaks occur in 5% of patients and are correlated with the use of warfarin and the presence of a patent inferior mesenteric artery preoperatively. They can be eliminated by endovascular coil embolization of the feeding arteries.

Renal failure from contrast nephropathy, intraoperative atheroemboli, or graft impingement on the main or accessory renal arteries is another possible complication of endovascular repair. Conversion to open repair because of aortic or iliac rupture, inability to gain access, error in positioning, inadequate fixation, or stent malfunction is rare (1–3%) if patients are properly screened preoperatively.

Prognosis

Mortality following elective open or endovascular repair is 1–5%. In general, a patient with an aortic aneurysm greater than 5 cm has a threefold greater chance of dying as a consequence of rupture of the aneurysm than of dying from surgical resection. Five-year survival after surgical repair is 60–80%. Another aortic aneurysm will develop adjacent to the graft or in the thoracic aorta in 5–10% of patients.

Brewster DC et al: Guidelines for the treatment of abdominal aortic aneurysms. Report of a subcommittee of the Joint Council of the American Association for Vascular Surgery and Society for Vascular Surgery. J Vasc Surg 2003;37:1106.

Fleming C et al: Screening for abdominal aortic aneurysm: a best-evidence systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2005;142:203.

Gorham TJ et al: Endovascular treatment of abdominal aortic aneurysm. Br J Surg 2004;91:815.

Greenhalgh RM et al; EVAR trial participants: Comparison of endovascular aneurysm repair with open repair in patients with abdominal aortic aneurysm (EVAR trial 1), 30-day operative mortality results: randomised controlled trial. Lancet 2004;364:843.

Lederle FA et al: Rupture rate of large abdominal aortic aneurysms in patients refusing or unfit for elective repair. JAMA 2002;287:2968.

Prinssen M et al: Dutch Randomized Endovascular Aneurysm Management (DREAM) Trial Group: a randomized trial comparing conventional and endovascular repair of abdominal aortic aneurysms. N Engl J Med 2004;351:1607.

Aneurysms of the Thoracic Aorta

Aneurysms of the thoracic aorta account for fewer than 10% of aortic aneurysms. Medial degeneration, chronic dissection, vasculitis, and collagen-vascular disease (Marfan's syndrome or Ehlers-Danlos syndrome) are common causes; syphilis is now a rare cause of thoracic aneurysm. Traumatic aneurysms occur at the ligamentum arteriosus just beyond the left subclavian artery and result from shearing injury during rapid-deceleration automobile accidents.

Thoracoabdominal aneurysms are categorized by the Crawford classification: type I extends from the left subclavian

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artery to the renal arteries, type II from the left subclavian artery to the iliac bifurcation, type III from the midthoracic to the infrarenal region, and type IV from the distal thoracic aorta to the infrarenal region. The prevalence of each type of thoracoabdominal aneurysm is roughly equal, but type IV aneurysms have the lowest operative mortality (2–5%) and the lowest risk of postoperative neurologic deficits (2–10%).

Clinical Findings

A. Symptoms and Signs

Clinical manifestations depend largely on the size and position of the aneurysm and its rate of growth. Most are asymptomatic and are discovered during a diagnostic procedure undertaken for other reasons. Some patients complain of substernal, back, or abdominal pain. Others experience dyspnea, stridor, or a brassy cough from pressure on the trachea, dysphagia from pressure on the esophagus, hoarseness from pressure on the left recurrent laryngeal nerve, or neck and arm edema from external compression of the superior vena cava. Aortic regurgitation due to distortion of the aortic valve annulus may occur with aneurysms of the ascending aorta.

B. Imaging

An aneurysm suspected on chest radiography must be differentiated from other anterior mediastinal masses, including lung neoplasm, thymoma, cyst, and substernal goiter. CT scan and MRI are the most sensitive and accurate means of imaging thoracic aneurysms. Aortography may be necessary to assess involvement of the arch vessels. The coronary vessels and the aortic valve should also be studied if aortic root replacement is anticipated.

Treatment

Control of hypertension and use of β-blockers may slow aneurysmal growth. Indications for surgical treatment include the presence of symptoms, rapid expansion, or size greater than 5 cm. Operative risk from comorbid medical conditions must be considered when recommending repair of asymptomatic aneurysms. Morbidity and mortality are higher than with abdominal aortic aneurysms; the 30-day operative mortality is 8–20% with repair of type I and type II thoracoabdominal aneurysms. The thoracotomy incision is associated with a higher risk of pulmonary complications and more challenging postoperative pain management. Proximity to the recurrent laryngeal nerve, the phrenic nerve, and the carotid and subclavian arteries makes injury to these structures possible. The great radicular artery (artery of Adamkiewicz) arises from an intercostal artery between T8 and L1 and is the dominant artery to the spinal cord in 80% of patients, imposing a 5–30% risk of paraplegia during thoracic aneurysm repair. Use of left heart bypass to femoral bypass to preserve retrograde perfusion below the level of the cross-clamp or antegrade perfusion by direct cannulation of selected arteries reduces end-organ ischemia. Lumbar drains have been proven to reduce the rate of paraplegia.

Endovascular repair of thoracic aortic aneurysms reduces cardiopulmonary risk, but the location of the aneurysm may preclude endovascular repair by current methods. Recent investigations involve development of branched stent grafts for repair of arch and thoracoabdominal aneurysms.

Prognosis

Five-year survival for patients with unrepaired thoracic aneurysms greater than 6 cm is 20–25%. Most deaths are due to rupture or to the complications of generalized atherosclerosis.

Hansen CJ et al: Complications of endovascular repair of high-risk and emergent descending thoracic aortic aneurysms and dissections. J Vasc Surg 2004;40:228.

Leurs LJ et al: EUROSTAR; UK Thoracic Endograft Registry collaborators: endovascular treatment of thoracic aortic diseases: combined experience from the EUROSTAR and United Kingdom Thoracic Endograft registries. J Vasc Surg 2004;40:670.

Peripheral Artery Aneurysms (Popliteal & Femoral)

Most lower extremity aneurysms occur in men over age 50 years. Half are bilateral. One-third of patients with popliteal aneurysms and one-half of those with femoral aneurysms have an associated aortoiliac aneurysm.

Popliteal Aneurysms

Popliteal aneurysms account for approximately 85% of all peripheral artery aneurysms. Symptoms are rarely due to rupture but result rather from arterial thrombosis, peripheral embolization, or compression of adjacent structures with resultant venous thrombosis or neuropathy. Arterial thrombosis can be limb-threatening if all outflow vessels are occluded, leading to amputation in up to 30% of patients.

Ultrasound is the diagnostic study of choice to measure the diameter of the aneurysm as well as to search for other arterial aneurysms. Magnetic resonance angiography (MRA) or conventional arteriography is required to define the anatomy of the outflow arteries in preparation for operative repair.

Surgery is recommended for all asymptomatic aneurysms larger than 2 cm and for all symptomatic aneurysms regardless of size. If preoperative angiography reveals no patent distal vessels for bypass, catheter-directed thrombolysis can be attempted. If a patent outflow vessel is identified or is recanalized with thrombolytic therapy, a saphenous vein bypass graft with proximal and distal ligation of the aneurysm is performed. In large aneurysms producing popliteal vein

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or nerve compression, resection of the aneurysm in addition to grafting is required.

Femoral Aneurysms

Femoral aneurysms present as pulsatile groin masses. They have the potential for the same complications as popliteal aneurysms. Because the incidence of complications is lower than with popliteal aneurysms, patients with combined disease undergo repair of aortoiliac and popliteal aneurysms before repair of the femoral aneurysm.

Femoral pseudoaneurysms may result from injury produced by injection drug abuse, femoral artery puncture for angiography, or femoral line insertion. Mycotic aneurysms must be widely debrided with proximal and distal ligation or interposition grafting using an autologous vein. Uninfected, small (< 5 cm) traumatic pseudoaneurysms can often be treated by ultrasound-guided compression of the neck of the aneurysm or by thrombin injection, which has a reported success rate of 90%. If these techniques are not successful, open repair is required. Pseudoaneurysms may also develop at the distal anastomosis of an aortofemoral bypass graft. They should be repaired if graft infection is suspected or if their diameter exceeds 2 cm.

Antonello M et al: Open repair versus endovascular treatment for asymptomatic popliteal artery aneurysm: results of a prospective randomized study. J Vasc Surg 2005;42:185.

Aulivola B et al: Popliteal artery aneurysms: a comparison of outcomes in elective versus emergent repair. J Vasc Surg 2004; 39:1171.

Kruger K et al: Femoral pseudoaneurysms: management with percutaneous thrombin injections—success rates and effects on systemic coagulation. Radiology 2003;226:452.

Marty B et al: Success of thrombolysis as a predictor of outcome in acute thrombosis of popliteal aneurysms. J Vasc Surg 2002;35:487.

Pittathankal AA et al: Expansion rates of asymptomatic popliteal artery aneurysms. Eur J Vasc Endovasc Surg 2004;27:382.

Visceral Aneurysms

Mesenteric, Hepatic, & Splenic Artery Aneurysms

Historically, mesenteric aneurysms had a high mortality rate because of delay in diagnosis. High-resolution CT scanning has increased the ability to detect incidental mesenteric aneurysms and has broadened our understanding of the disease. In the last decade, hepatic artery aneurysms have become the most common of the visceral artery aneurysms, superseding splenic artery aneurysms, which now comprise less than 40% of the total. Superior mesenteric, celiac, gastric, and gastroepiploic artery aneurysms each represents about 5% of visceral aneurysms. Aneurysms of mesenteric branch vessels are rare and are often associated with connective tissue disease or vasculitis.

Medial degeneration is the most commonly cited cause of hepatic aneurysms. Increasingly, however, injury during cholangiography, hepatic biopsy, or blunt abdominal trauma is implicated—particularly in intrahepatic aneurysms, which account for about half of all hepatic aneurysms. Splenic artery aneurysms are most commonly related to medial fibroplasia, though portal hypertension, splenomegaly, pregnancy, and local inflammation (eg, pancreatitis) have all been implicated as possible risk factors. These aneurysms occur four times more frequently in women than in men, underscoring possible hormonal influences. Most superior mesenteric artery aneurysms are associated with infective endocarditis and suspected septic emboli. Atherosclerosis may play a role in the pathogenesis of celiac artery aneurysms—and a secondary role in development of other mesenteric aneurysms.

Surgical (aneurysmectomy or aneurysmorrhaphy with ligation of branches) or endovascular (embolization or stent graft repair) management is warranted for symptomatic aneurysms and aneurysms over 2 cm in diameter. Asymptomatic splenic aneurysms less than 2 cm in diameter rarely rupture, and treatment is not generally advised unless the patient is pregnant or anticipates becoming pregnant since the highest risk of rupture is in young women during pregnancy.

Abbas MA et al: Hepatic artery aneurysm: factors that predict complications. J Vasc Surg 2003;38:41.

Grego FG et al: Visceral artery aneurysms: a single center experience. Cardiovasc Surg 2003;11:19.

Morimoto N et al: Inferior mesenteric artery aneurysm in Behcet syndrome. J Vasc Surg 2003;38:1434.

Stambo GW et al: Coil embolization of multiple hepatic artery aneurysms in a patient with undiagnosed polyarteritis nodosa. J Vasc Surg 2004;39:1122.

Renal Artery Aneurysms

Renal artery aneurysms have a reported incidence of about 1% in the adult population. Many renal artery aneurysms are asymptomatic and diagnosed as an incidental finding on CT scan or angiography performed for another purpose. Others are found during evaluation for hematuria, renal infarct, flank pain, or suspected renovascular hypertension. Five percent of renal artery aneurysms present with rupture. Fibromuscular dysplasia is present in about 40% of patients; another 25% have atherosclerosis. Medial degeneration, trauma, and injury after renal biopsy or percutaneous nephrolithostomy are other potential causes. Indications for treatment include size greater than 2 cm, local symptoms, renovascular hypertension, distal embolization, growth on serial imaging, or aneurysms in women of childbearing age.

The standard surgical approach for renal artery aneurysms is excision with interposition grafting; infrequently, the aneurysm extends into the branch vessels, and ex vivo reconstruction may be required. Autologous and prosthetic materials have been equally effective for interposition grafting of main renal arteries greater than 5 mm in diameter, with a 5-year primary

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patency rate approaching 90%. Recently, polytetrafluoroethylene-covered stent grafts have been used for treatment of saccular aneurysms of the main renal artery. Interlobar aneurysms can be treated by endovascular embolization with microcoils.

English WP et al: Surgical management of renal artery aneurysms. J Vasc Surg 2004;40:53.

Pershad A et al: Renal artery aneurysm: successful exclusion with a stent graft. Catheter Cardiovasc Interv 2004;61:314.

Aortic Dissection

Essentials of Diagnosis

  • A history of hypertension or Marfan's syndrome is often present.

  • Sudden severe chest pain with radiation to the back, occasionally migrating to the abdomen and hips.

  • Patient appears to be in shock, but blood pressure is normal or elevated; pulse discrepancy in many patients.

  • Acute aortic regurgitation may develop.

General Considerations

Aortic dissection is the most common aortic catastrophe requiring admission to a hospital. It is caused by an intimal tear, which allows creation of a false lumen between the media and adventitia. Over 95% of intimal tears occur either in the ascending aorta just distal to the aortic valve (Stanford type A) or just distal to the left subclavian artery (Stanford type B). These are points where the aorta is fixed and allow for intimal injury during shear stress. The false lumen can rupture into the pericardial sac, left pleural space, or retroperitoneum. More commonly, the dissection propagates distally to involve aortic branch vessels, producing acute spinal cord (3%), visceral (9%), renal (12%), or lower extremity (9%) ischemia. Proximal extension of a type A dissection can stretch the aortic annulus or occlude a coronary artery orifice, producing acute aortic regurgitation, myocardial infarction, and intrapericardial rupture with tamponade. Both blood pressure and the rate of acceleration of pulsatile flow (dP/dt) are important in propagation of dissection; 80% of patients with acute dissection are hypertensive. Other risk factors for dissection are Marfan's syndrome, pregnancy, bicuspid aortic valve, and coarctation of the aorta.

When not appropriately diagnosed and treated, type A aortic dissection is a lethal disease. Untreated type A dissections are associated with 50% mortality at 48 hours and 90% mortality at 1 month—due to free rupture, tamponade, or acute left ventricular failure. Mortality with untreated type B dissection is 10–20%, usually secondary to free rupture into the pleural space, acute mesenteric ischemia, or renal failure.

Clinical Findings

A. Symptoms and Signs

Eighty-five percent of patients report sudden excruciating (“ripping”) pain in the chest or upper back. The pain may radiate into the abdomen, neck, or groin. Many patients are hypertensive at presentation. Some present with syncope, hemiplegia, or lower extremity paralysis. On physical examination, peripheral pulses and blood pressures may be diminished or unequal. A diastolic murmur of aortic insufficiency may be heard.

B. Laboratory Findings

The ECG may be normal but often reveals left ventricular hypertrophy from long-standing hypertension. Acute ischemic changes suggest coronary artery involvement. Because dissections preferentially extend into the right coronary ostium, inferior wall abnormalities predominate.

C. Imaging

Chest radiographs often reveal—in comparison with previous films—an abnormal aortic contour or a widened superior mediastinum. Pleural or pericardial effusion may be present. Dynamic CT scanning, angiography, MRI, and transesophageal echocardiography (TEE) have all been used to diagnose acute dissection. TEE is favored because of its high sensitivity (98%) and specificity (99%) and because it can be performed rapidly and at the bedside. The best initial study is the one most readily available that can be interpreted accurately in a given hospital setting. MRI has not played a major role in the initial diagnosis but is useful for serial follow-up.

Differential Diagnosis

Acute myocardial infarction, pulmonary embolism, esophageal disruption, strangulated paraesophageal hernia, mesenteric ischemia, and symptomatic aortic aneurysm may all be considered in the differential diagnosis of acute aortic dissection.

Treatment

A. Medical Treatment

Aggressive blood pressure control should be initiated immediately. Treatment is targeted to reduce aortic pressure and pulsatile flow (dP/dt). This is accomplished by lowering systemic vascular resistance and cardiac output (primarily heart rate).

Systemic vascular resistance is reduced by means of a rapid-acting antihypertensive agent titrated by intravenous infusion to maintain a systolic blood pressure

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of 100–120 mm Hg. Possible medications include nitroprusside (0.3–10 mcg/kg/min), which causes direct vasodilation by its action on smooth muscle nitric oxide pathways, or fenoldopam (0.1–1.6 mcg/kg/min), which acts as an agonist of D1-dopamine receptors. When nitroprusside is continued for 48 hours or more, thiocyanate levels should be checked and the infusion stopped if the level is over 10 mg/dL (to avoid toxicity).

The heart rate is decreased by administering the selective β1-adrenergic antagonist esmolol (50–300 mcg/kg/min intravenously) and by intermittent administration of metoprolol (5–10 mg intravenously every 15 minutes) or the α1- and nonselective β-antagonist labetalol (20–80 mg intravenously every 10 minutes or 1–2 mg/min).

Long-term drug therapy for aortic dissections involves use of a β-antagonist (eg, metoprolol, 25–100 mg orally twice daily; atenolol, 50–100 mg orally daily), often in combination with another antihypertensive agent such as the centrally acting α2-agonist clonidine (0.1–0.3 mg orally twice daily or 0.1–0.3 mg transdermal patch topically every 24 hours) or the direct vasodilator hydralazine (10–50 mg orally four times daily); the calcium channel blocker amlodipine (2.5–10 mg orally daily); or the angiotensin-converting enzyme inhibitor enalapril (2.5–20 mg orally daily).

B. Surgical Treatment

All patients with type A dissection should undergo emergent surgical repair. Most patients with type B dissection can be managed initially with aggressive drug therapy. Indications for surgical treatment of type B dissections are aortic rupture; severe intractable pain; mesenteric, renal, or limb ischemia; and progression of the dissection. For type A dissection, the ascending aorta and, if necessary, the aortic valve and arch are replaced with reimplantation of the coronary and brachiocephalic vessels. The mortality rate for such operations approaches 20%. Type B dissection with ischemic complications is treated by obliteration of the false lumen and/or secondary arterial bypass if this fails to restore blood flow to the ischemic organs. Several different techniques have been described for obliteration of the false lumen: resection of the entry point of the dissection and prosthetic tube graft interposition, open or endovascular fenestration of the dissection flap, or stent graft deployment to cover the entry point. Use of felt strips or instillation of tissue glue into the false lumen during open repair can strengthen the dissected aortic wall.

Surgical indications and risks for chronic type B dissections are the same as for degenerative thoracoabdominal aneurysms. Repair is considered in symptomatic patients or patients with aneurysms larger than 5 cm. Reported surgical mortality is 5–30%. For this reason, long-term drug therapy may be the preferred treatment for patients with significant comorbidities.

Prognosis

Because of comorbid illnesses, operative mortality of patients with type B dissection is twice that of patients with type A dissection. After hospital discharge, 5-year survival is 70–80% for repaired type A and 50–70% for repaired type B dissections. In some medically treated type B dissections, the false lumen thromboses and eventually heals with minimal dilation. In others, a chronic dissection results in a progressively enlarging aneurysm requiring eventual repair in up to 30% of patients. For this reason, all unoperated patients should be monitored with annual CT scan or MRI.

Aziz S et al: Acute dissection of the thoracic aorta. Hosp Med 2004;65:136.

Clouse WD et al: Acute aortic dissection: population-based incidence compared with degenerative aortic aneurysm rupture. Mayo Clin Proc 2004;79:176.

Hansen CJ et al: Complications of endovascular repair of high-risk and emergent descending thoracic aortic aneurysms and dissections. J Vasc Surg 2004;40:228.

Knaut AL et al: Aortic emergencies. Emerg Med Clin North Am 2003;21:817.

Mehta RH et al: International Registry of Acute Aortic Dissection Investigators: acute type B aortic dissection in elderly patients: clinical features, outcomes, and simple risk stratification rule. Ann Thorac Surg 2004;77:1622.

Roseborough G et al: Twenty-year experience with acute distal thoracic aortic dissections. J Vasc Surg 2004;40:235.

Suzuki T et al: Clinical profiles and outcomes of acute type B aortic dissection in the current era: lessons from the International Registry of Aortic Dissection (IRAD). Circulation 2003;108(Suppl 1):II312.

Tan ME et al: Operative risk factors of type A aortic dissection: analysis of 252 consecutive patients. Cardiovasc Surg 2003; 11:277.

Yu HY et al: Late outcome of patients with aortic dissection: study of a national database. Eur J Cardiothorac Surg 2004; 25:683.

Lower Extremity Occlusive Disease

Occlusive disease of the lower extremities is present in 8–12 million persons in the United States and is an important cause of disability. It is also a predictor of all-cause mortality and an independent risk factor for cardiovascular morbidity and mortality; patients with intermittent claudication have a 2.5 times higher risk of cardiac events than that of an age-matched population. Severe triple-vessel coronary artery disease is found in almost 30% of patients undergoing routine coronary catheterization prior to peripheral bypass. Vascular endothelial dysfunction is a systemic phenomenon and a marker for atherosclerosis; impairment of flow-mediated dilation in the peripheral arteries

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has been shown to correlate with the presence of coronary artery disease. It is essential for the primary care clinician to emphasize prevention of disease, particularly in light of what is known about etiologic factors.

DeBakey first characterized the distribution of atherosclerotic disease in the lower extremity. Plaque formation predominates at the aortic bifurcation, at the tibial trifurcation, and in the superficial femoral artery at the adductor hiatus. Interestingly, occlusive disease often spares the internal iliac, profunda, and peroneal arteries. Three distinct patterns of disease have since been described. Type 1 disease affects about 10–15% of patients and is limited to the aorta and common iliac arteries. It is most commonly found in younger men and women (ages 40–55 years) who are heavy smokers or who have hyperlipidemia. Type 2 disease (25% of patients) involves the aorta, the common iliac artery, and the external iliac artery. Type 3 disease is the most common (60–70% of patients) and is multilevel disease, affecting the aorta and the iliac, femoral, popliteal, and tibial arteries. Patients with type 2 and type 3 patterns of disease have typical risk factors for atherosclerosis: older age, male gender, diabetes, and hypertension. They also have a high incidence of coexisting cerebrovascular and coronary artery disease.

Clinical Findings

A. Symptoms and Signs

Lower extremity occlusive disease is manifested by several different clinical presentations: erectile dysfunction, claudication, rest pain, and gangrene. The symptoms and physical examination predict the location and severity of disease. Occlusive disease of the iliac arteries can produce male erectile dysfunction. The triad of bilateral hip and buttock claudication, erectile dysfunction, and absent femoral pulses is known as Leriche's syndrome.

Claudication is characterized by fatigue, pain, or weakness in the calves, thighs, or buttocks brought on by walking and completely relieved after a few minutes of rest. The reproducibility of these symptoms helps differentiate claudication from other causes of leg pain such as radiculopathy and musculoskeletal disorders. Ischemic rest pain, defined as pain in the absence of exertion, is usually described as a nocturnal pain located across the dorsum of the foot at the metatarsal heads. It can be reduced by placing the legs in the dependent position, usually by hanging them over the side of the bed. Rest pain, ischemic ulceration, or gangrene implies impending limb loss.

Examination of the pulses indicates the level of disease. Absent or weak femoral pulses or the presence of an iliac or femoral bruit suggests inflow disease. Similarly, normal femoral pulses but a diminished or absent popliteal pulse is indicative of superficial femoral artery stenosis and normal femoral and popliteal pulses and nonpalpable dorsalis pedis or posterior tibial pulse indicate tibial disease. An ankle-brachial index (ABI) is useful in gauging the degree of arterial insufficiency. A normal ratio of ankle to brachial systolic blood pressures is 1.0; less than 0.8 is consistent with claudication. Exercise, which lowers the ABI by exaggerating the difference in brachial and ankle blood pressures, can sometimes aid in detection of occlusive disease. Rest pain and nonhealing ulcers are common with an ABI less than 0.4. A toe-brachial index (TBI) can be used in diabetic or renal failure patients when an ABI cannot be obtained because the tibial arteries are calcified and noncompressible. A penile-brachial index (PBI) is obtained when vasogenic impotence is suspected. A PBI less than 0.6 suggests significant arterial disease. These measurements can also be used to monitor progression of disease and to assess the effect of therapeutic intervention.

Other findings on physical examination include atrophy of the skin, subcutaneous tissues, and muscles of the calf. Dependent rubor, hair loss, and coolness of the skin are signs of advanced ischemia. Ulcers from arterial occlusive disease are painful, well-circumscribed lesions generally located over pressure points, such as the first metatarsal head or heel. Ulcers that have failed to heal with 3 months of appropriate local wound care and ulcers associated with an ABI less than 0.3 are unlikely to heal without treatment to improve arterial blood flow and tissue perfusion.

B. Imaging

Catheter or MRA demonstrates the extent of the disease and the condition of the distal target vessels for potential bypass operation. The standard study images the infrarenal aorta and iliacs (including oblique views of the pelvis and groin to visualize the origins of the hypogastric and profunda arteries), the runoff vessels, and the foot in a lateral position. Angiography is undertaken only for percutaneous treatment or in preparation for surgical intervention. Gadolinium-enhanced MRA is used in the evaluation of lower extremity occlusive disease, particularly in patients with renal insufficiency. Ultrasound is also used in routine follow-up of infrainguinal bypass grafts to screen for graft stenoses amenable to prophylactic angioplasty or segmental replacement. Radiographs of the lower leg and foot are often obtained to rule out osteomyelitis underlying an infected ulcer or to identify severe calcification of potential runoff vessels.

Treatment

A. Conservative Measures

Treatment of claudication begins with identification and control of risk factors and initiation of an exercise program. Tobacco cessation slows the rate of progression of arterial occlusive disease and reduces cardiovascular mortality. Lipid-lowering medications have been shown to produce a 40% risk reduction for new-onset claudication or worsening of claudication. A supervised,

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dedicated walking program sustained over 3–6 months has been shown to increase pain-free walking distance by as much as 150%. Exercise improves symptoms by increasing muscle anaerobic metabolism and shifting the energy of walking to muscles with higher oxygen delivery. A standard program is structured as four 30-minute sessions per week: walking along flat ground until discomfort occurs, resting until it subsides, and then resuming walking.

The main drug used in therapy is the phosphodiesterase inhibitor, cilostazol (100 mg orally twice daily), which impairs platelet aggregation, increases calcium-mediated vasodilation, and has been shown to increase walking distance by 34% more than placebo. It is contraindicated in patients with heart failure and is not well tolerated in about 20% of patients due to side effects of headache, dizziness, and diarrhea. Propionyl-L-carnitine (1000 mg orally twice daily) has also been correlated with increased walking distance in patients with claudication. Its mechanism of action is unknown; it may improve skeletal muscle metabolism. Ginkgo biloba extract (120 mg/d) is an herbal medication with some reported benefit in claudication (see Chapter 42). It has been correlated with an increased risk of bleeding and so should be used with caution in patients on warfarin or clopidogrel. Aspirin (325 mg orally daily) is routinely prescribed for all patients who do not have drug allergy or intolerance. It is continued indefinitely after angioplasty or surgery to decrease thrombotic complications and impede progression of intimal hyperplasia. Clopidogrel (75 mg orally daily) or warfarin (dosed to maintain an INR of 2.0–3.0) may be selected for postoperative patients perceived to have a higher risk of graft thrombosis due to a hypercoagulable state, suboptimal conduit, or poor distal runoff.

Treatment of male erectile dysfunction requires evaluation of its possible causes (medications, diabetes mellitus, psychogenic factors, and arterial occlusive disease). Iliac or dorsal penile artery revascularization can be beneficial in some cases of vasculogenic impotence. Other patients may respond to sildenafil, 25–50 mg 30 minutes to 4 hours prior to sexual activity. It is contraindicated in patients taking nitroglycerin because of the risk of myocardial ischemia due to hypotension (see Chapter 23).

B. Surgery

Percutaneous or open operation is considered for good-risk patients with short-distance (less than two blocks) claudication that impairs their ability to work or perform activities of daily living. Development of rest pain or tissue loss indicates progression of disease and also warrants evaluation for limb revascularization.

Because many of these patients have coexisting ischemic heart disease, medical management should be optimized preoperatively. The roles of exercise testing and coronary angiography are discussed in Chapters 3 and 10. The carotid arteries should be imaged by ultrasound; endarterectomy may be indicated to minimize perioperative risk of stroke.

1. Endovascular techniques

Common iliac artery stenoses are often amenable to percutaneous treatment. Stent angioplasty has been shown to decrease recurrence rates seen with angioplasty alone; most recent studies report a 70–80% 3-year patency rate with self-expanding (Wall) stents or balloon-expandable (Palmaz) stents. Stenting of distal lesions (external iliac or infrainguinal arteries) is not as successful, with reported 3-year primary patency rates of 55–60%. Stents do not appear to confer added benefits over angioplasty alone for femoral-popliteal lesions except in cases of postangioplasty arterial dissection or successfully recanalized short-segment arterial occlusion. Ideal lesions for angioplasty are discrete, short-segment (< 5 cm in length), concentric lesions in noncalcified large-diameter vessels. Often, endovascular techniques are used in conjunction with surgery for treatment of multifocal lower extremity occlusive disease such as an iliac stent being placed at the time of an ipsilateral femoral popliteal bypass. Some surgeons are evaluating long-segment closed superficial femoral artery endarterectomy combined with distal stenting as an alternative to femoral popliteal bypass in high-risk surgical patients with suboptimal vein available for bypass conduit. Few groups have achieved favorable results with percutaneous atherectomy devices or laser probes.

2. Open surgery

Aortobifemoral bypass grafting using a synthetic prosthesis is the standard treatment for complex aortoiliac occlusive disease. In general, a bifurcated polytetrafluoroethylene or Dacron graft is anastomosed end to end with the infrarenal abdominal aorta and end to side to each common femoral artery. If both external iliac arteries are occluded, an end-to-side aortic anastomosis preserves inflow into the internal iliac arteries. For high-risk patients, an axillary-femoral or femoral-femoral bypass graft can be considered, though such extra-anatomic grafts have lower long-term patency than bypass grafting (50% versus 80% at 10 years).

For infrainguinal occlusive disease, the bypass conduit of choice is the autogenous greater saphenous vein. Five-year patency rates of 75–80% can be achieved with vein bypasses to the dorsalis pedis artery or the posterior tibial artery at the ankle. By contrast, the 5-year patency of femoral-tibial bypasses performed with synthetic conduit is less than 40%. Some surgeons prefer prosthetic graft for femoral-to-above-knee-popliteal artery bypasses, as the reported long-term patency in this position is almost equivalent to that of vein graft. Others maintain an “all autogenous” policy for all infrainguinal bypass grafts. In as many as 30% of patients, the greater saphenous vein is inadequate because it is sclerotic, thrombosed, or less than 3 mm in diameter or because the patient has undergone varicose vein stripping or saphenous vein harvesting for coronary artery bypass or previous leg bypass. Alternative

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conduits in these patients include the lesser saphenous vein, arm vein, cryopreserved homologous vein, or prosthetic graft with a distal vein cuff.

Other determinants of long-term graft patency include quality of arterial inflow, patency of runoff arteries, and length of the bypass conduit. It is imperative to address any flow-limiting aortoiliac disease before performing any infrainguinal bypass.

Thromboendarterectomy involves resecting the thickened intima and media from the diseased artery and is an alternative to bypass for short-segment lesions in larger arteries. It can be used in type 1 disease to obviate the need for prosthetic graft. Common femoral or profunda femoral thromboendarterectomy is combined with distal bypass to improve inflow.

Operative mortality is 2–5% for open aortic surgery and 1–3% for infrainguinal bypass, largely attributable to cardiac complications. Risks specific to aortic surgery include renal insufficiency, bowel ischemia, impotence or retrograde ejaculation, and blue toe syndrome secondary to distal emboli. Late complications include graft thrombosis, graft infection, and aortoduodenal fistula. Complications of percutaneous techniques include problems at the puncture site (hematoma, pseudoaneurysm, arteriovenous fistula, retroperitoneal hemorrhage, occlusion), dissection or rupture of the artery during angioplasty, distal emboli from catheter manipulation, and contrast nephropathy. Patients with chronic renal insufficiency (serum creatinine > 1.5 mg/dL) undergoing angiography may be pretreated with intravenous hydration and acetylcysteine, 400 mg orally twice daily for 48 hours before and after contrast administration.

Prognosis

Ischemic rest pain or ulceration will eventually develop in 25% of patients with claudication; approximately 10% will require amputation. In part, the high rate of limb salvage reflects a high mortality rate from comorbid disease. Because of coronary artery disease, patients with claudication have a 5-year survival of 50%. For this reason, surgery is generally deferred until failure of drug therapy and exercise programs and impairment of activities of daily living.

The overall 5-year patency rate for infrainguinal saphenous vein grafts is 60–80%. Higher graft patency and limb salvage rates are achieved with suprageniculate bypasses and with patients presenting with claudication rather than rest pain or gangrene. Graft occlusion may convert a patient with claudication to one with limb-threatening ischemia because of loss of collateral flow. Conversely, a patient who undergoes bypass for distal gangrene may have a clinically silent graft occlusion after the ulcer heals. Surveillance duplex ultrasound is advised at 6-month intervals to detect stenotic, or “threatened,” grafts before they progress.

Bachoo P et al: Endovascular stents for intermittent claudication. Cochrane Database Syst Rev 2003;(1):CD003228.

Gey DC et al: Management of peripheral arterial disease. Am Fam Physician 2004;69:525. Erratum in Am Fam Physician 2004;69:1863.

McDermott MM et al: Functional decline in peripheral arterial disease: associations with the ankle brachial index and leg symptoms. JAMA 2004;292:453.

Peripheral Arterial Diseases Antiplatelet Consensus Group: Antiplatelet therapy in peripheral arterial disease. Consensus statement. Eur J Vasc Endovasc Surg 2003;26:1.

Raines JK et al: Ankle/brachial index in the primary care setting. Vasc Endovasc Surg 2004;38:131.

Tran H et al: Oral antiplatelet therapy in cerebrovascular disease, coronary artery disease, and peripheral arterial disease. JAMA 2004;292:1867.

Unusual Causes of Popliteal Artery Occlusion

The most common cause of popliteal artery occlusion is athero-occlusive disease. Thrombosis of a popliteal aneurysm can also cause popliteal occlusion and acute leg ischemia. Claudication in a young, athletic individual with no risk factors for atherosclerosis and normal pedal pulses may suggest popliteal entrapment syndrome, popliteal adventitial cystic disease, trauma, or extrinsic compression by a Baker cyst.

Popliteal entrapment syndrome is a group of anatomic anomalies that leads to popliteal arterial compression. Type 1 (20% of patients) is produced by an abnormal course of the popliteal artery, passing medial to the medial head of the gastrocnemius muscle. Type 2 (25%) is caused by medial insertion of the medial head of the gastrocnemius muscle. The popliteal artery is compressed by an abnormal accessory slip of gastrocnemius muscle in type 3 (30%) or popliteus muscle in type 4 (8%). Almost 30% of patients have bilateral disease. Claudication symptoms may be atypical, such as pain with walking but not with running. Diagnosis is made by MRA or by positional angiography; the patent artery becomes impinged with passive dorsiflexion or active plantar flexion of the ankle. Treatment is surgical and involves transection of the abnormal muscle; if the artery is injured or occluded, short-segment bypass with the greater saphenous vein is required.

Popliteal adventitial disease is a rare disorder of unknown cause characterized by formation of cysts within the wall of the popliteal artery. The cysts compress the arterial lumen, causing stenosis or occlusion. Their contents resemble synovial fluid, and some may be in continuity with the joint space. The disease most often affects healthy men 40–50 years of age. Larger cysts are amenable to ultrasound-guided aspiration, but most are small and appear only as a thickening of the popliteal artery wall on MRA. In these cases, bypass or interposition grafting is curative.

Elias DA et al: Clinical evaluation and MR imaging features of popliteal artery entrapment and cystic adventitial disease. AJR Am J Roentgenol 2003;180:627.

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Occlusive Cerebrovascular Disease

Every year, half a million people in the United States suffer a stroke. Fifteen to 30 percent of these episodes are fatal, making stroke the third leading cause of death in this country. Carotid artery stenosis is responsible for as many as 25% of these strokes in the elderly. Most neurologic events are caused by emboli occluding small cerebral arteries. Emboli from the carotid bifurcation may consist of platelet aggregates that form on irregular or ulcerated surfaces or plaque debris liberated by turbulent flow and intraplaque hemorrhage. Less commonly (less than 10% of cases), emboli arise from the heart (eg, mural thrombus or atrial myxoma) or from the aortic arch. Stroke can also be caused by intracerebral hemorrhage (from trauma or a ruptured cerebral aneurysm) or by small vessel occlusive disease in the pons, basal ganglia, and internal capsule of the brain (lacunar infarcts).

A transient ischemic attack (TIA) is defined as the sudden onset of a neurologic deficit that resolves completely within 24 hours. A stroke is a neurologic deficit that persists beyond 24 hours. A single TIA or stroke is associated with a 30% risk of subsequent stroke.

Risk factors for carotid disease include hypertension, diabetes mellitus, hypercholesterolemia, advanced age, smoking, and coronary artery disease.

Clinical Findings

A. Symptoms and Signs

Clinical manifestations of carotid artery occlusive disease include contralateral weakness or sensory loss, expressive aphasia, and amaurosis fugax (transient partial or complete loss of vision in the ipsilateral eye). Vertebrobasilar TIAs are characterized by brainstem and cerebellar symptoms, including dysarthria, diplopia, vertigo, ataxia, and hemiparesis or quadriparesis.

Dizziness and unsteadiness, particularly when associated with a quick change in position, are nonspecific symptoms and more often the result of postural hypotension than of vertebrobasilar insufficiency. Syncope is rarely a manifestation of carotid artery occlusive disease. Rather, it is usually a result of a cardiac arrhythmia.

Occlusive disease of the brachiocephalic arteries may be accompanied by cervical bruits, diminished or absent pulses in the neck or arms, Hollenhorst plaques (bright, refractile cholesterol emboli) in the retinal arteries, or a blood pressure difference between the two arms of more than 10 mm Hg. The common carotid pulsation can be examined qualitatively by palpation at the base of the neck. The presence of superficial temporal artery pulsation confirms patency of the ipsilateral external carotid artery. A carotid bruit is a high-pitched, blowing noise localized in the mid neck close to the angle of the mandible. Heart sounds must be auscultated to make certain that the bruit is not caused by a referred murmur of aortic stenosis. Only 30% of patients with cervical bruits have carotid stenosis greater than 60%. The absence of a bruit also does not preclude the possibility of a hemodynamically significant lesion—thus, bruits are neither sensitive nor specific for carotid occlusive disease. In fact, asymptomatic carotid bruits are stronger predictors of death from coronary artery disease than of death from stroke.

B. Imaging Studies

Duplex ultrasonography has become the study of choice for evaluation of carotid occlusive disease. It provides both physiologic and anatomic information. Percent stenosis is derived from measurement of blood flow velocities, with sensitivity and specificity greater than 90%. Ultrasound also provides some characterization of the plaque itself, including its location and the presence of calcification, ulceration, and intraplaque hemorrhage. Patients with adequate ultrasound studies may be offered surgery without further imaging. Patients with suboptimal ultrasound studies or in whom intracranial tandem lesions may be suspected are referred for gadolinium-enhanced MRA, which provides more detailed information about plaque composition and characterizes the intracranial circulation and the brain parenchyma. When compared with en bloc resected specimens, correlation of percent stenosis is better with ultrasound and MRA than with conventional angiography. This can be explained by the fact that MRA and ultrasound both produce cross-sectional imaging of vessels whose stenotic regions may be eccentric. Symptomatic patients with ipsilateral carotid occlusion by ultrasound should be referred for conventional or CT angiography before electing nonoperative management because a small percentage of these patients will have an internal carotid artery “string sign” and should be revascularized. Catheter angiography carries a 1% risk of procedure-related stroke and is reserved for patients with greatly disparate ultrasound and MRA findings, those suspected of vertebrobasilar insufficiency or intracranial lesions unable to undergo MRA, and those potentially requiring endovascular intervention. As ultrasound is highly operator dependent, whereas MRA is highly equipment dependent, selection of the most accurate imaging modality may vary by institution.

Treatment

A. Medical Measures

Acute or evolving strokes and strokes associated with major neurologic deficits are initially managed medically, delaying surgery for 5–8 weeks until the deficit is stable, as discussed in the section on cerebrovascular accidents in Chapter 24. Patients with TIAs may be treated initially with an oral antiplatelet medication (aspirin, 81 mg daily, or clopidogrel, 75 mg daily) to reduce the likelihood of thrombosis and microemboli and then scheduled for elective surgery. However, if

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the attacks are of increasing frequency, the patient is admitted, and intravenous heparin is started while the patient is evaluated for surgery. Postoperatively, most patients are maintained on aspirin indefinitely to reduce the incidence of thrombosis or recurrent disease in the newly endarterectomized vessel.

For patients in whom neurologic symptoms are thought to be secondary to intracerebral disease not amenable to surgical reconstruction, warfarin or clopidogrel may be indicated.

B. Surgery

1. TIAs and stroke

Carotid endarterectomy plus optimal drug therapy and risk factor modification are highly effective in preventing stroke and death in symptomatic patients with carotid stenosis greater than 70%—as demonstrated by the North American Symptomatic Carotid Endarterectomy Trial (NASCET). A more modest risk-benefit ratio has been demonstrated for carotid endarterectomy in symptomatic 50–69% stenoses. Surgical success is maximized when preoperative symptoms are related to ischemia of the ipsilateral hemisphere and when the surgery is done by a vascular surgeon who performs carotid endarterectomies regularly with a mortality-complication rate less than 5%. Placement of a temporary carotid shunt during surgery may be necessary to allow cerebral perfusion during cross-clamping. Indications for intraoperative shunting vary by surgeon. Most surgeons shunt patients with previous stroke; some selectively shunt for a measured stump pressure (internal carotid back pressure) under 50 mm Hg or for patients with electroencephalogram (EEG) changes, and others shunt all patients.

2. Asymptomatic carotid stenosis

Patients with asymptomatic carotid stenosis greater than 80% have a 12% risk of stroke. This statistic helps form the basis for the American Heart Association's recommendation of upper limits of acceptable combined morbidity and mortality for carotid endarterectomy: 3% for asymptomatic patients, 5–7% for those with TIAs or stroke, and 10% for those with recurrent carotid stenosis. The Asymptomatic Carotid Artery Stenosis (ACAS) trial demonstrated that in good-risk asymptomatic patients with greater than 60% stenosis, surgery afforded an overall relative risk reduction of 53% over aspirin alone. These findings are supported by a smaller Veterans Administration Hospital study of patients with asymptomatic carotid artery stenosis. Most vascular surgeons offer surgery to good-risk asymptomatic patients with greater than 80% stenosis in the ipsilateral carotid artery.

3. Percutaneous techniques

Patients who are not good candidates for surgery because of medical comorbidities can be considered for carotid angioplasty and stenting. This is also an option in patients with a history of previous neck surgery or irradiation, in whom there is a higher risk of cranial nerve injury because of fibrosis and scarring. Carotid stenting is associated with a 2–18% risk of periprocedural stroke or TIA and an 8–14% per year incidence of recurrent stenosis (compared with less than 4% per year with surgery). Recent trials suggest that complications after carotid stenting may be similar to those after open endarterectomy.

Prognosis

Carotid endarterectomy carries a reported average 1–2% mortality rate and a 1–5% risk of neurologic complication, though institutional variation exists. In symptomatic patients, endarterectomy reduces stroke risk fivefold to tenfold at 5 years. The 5–15% incidence of late stroke after uncomplicated endarterectomy is often related to contralateral carotid or intracranial disease.

Restenosis occurring less than 2 years after carotid endarterectomy is usually not symptomatic because it is due to intimal hyperplasia, which produces a smooth, nonfriable luminal surface. These lesions respond well to angioplasty and stenting, and the risk of procedural neurologic events is lower than for atherosclerotic lesions. Such lesions may regress and intervention is reserved for stenoses of 80% or greater. After 2 years, restenosis is more often related to progression of atherosclerotic disease. These lesions can be friable and prone to intraplaque hemorrhage, just like the original plaque. In general, repeat surgery or stenting is advised for symptomatic restenoses or stenoses greater than 80%.

Albers GW et al: Antithrombotic and thrombolytic therapy for ischemic stroke: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3 Suppl):483S.

Collins R et al: Heart Protection Study Collaborative Group: effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet 2004;363:757.

Coward LJ et al: Percutaneous transluminal angioplasty and stenting for carotid artery stenosis. Cochrane Database Syst Rev 2004;(2):CD000515.

Halliday A et al: MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group: prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet 2004;363:1491. Erratum in Lancet 2004;364:416.

Mas JL et al: EVA-3S Investigators: carotid angioplasty and stenting with and without cerebral protection: clinical alert from the Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis (EVA-3S) trial. Stroke 2004;35:e18.

Meyers PM et al: Use of stents to treat extracranial cerebrovascular disease. Ann Rev Med 2006;57:437.

Rothwell PM et al: Carotid Endarterectomy Trialists Collaboration: endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet 2004;363:915.

Yadav JS et al: Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy Investigators: protected carotid-artery stenting versus endarterectomy in high-risk patients. N Engl J Med 2004;351:1493.

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Other Diseases of the Carotid Artery

Carotid Dissection

Carotid dissection is a false channel in the wall of the carotid artery produced by a tear in the intima. The classic triad of symptoms is unilateral neck pain or headache, stroke or TIA, and an incomplete Horner syndrome (miosis and ptosis without anhidrosis). Dissections can be spontaneous or traumatic, caused by shearing of the internal carotid artery between the C2 and C3 transverse processes during deceleration injuries such as car accidents, wrestling, or chiropractic maneuvers. The primary treatment of dissection is drug therapy. With warfarin anticoagulation (to an INR of 2.0–3.0), 60–85% of carotid dissections will heal in 3–6 months with complete or near-complete neurologic recovery. Recurrent dissection is estimated at 3% at 3 years and 12% at 10 years and most often involves a different cervical vessel, which justifies the use of long-term aspirin. Surgery (usually carotid interposition) or carotid stenting is indicated for persistent symptoms despite optimal drug therapy.

Carotid Body Tumors

The carotid body is a chemoreceptor derived from embryonic neural crest cells located at the carotid bifurcation. Carotid body tumors (also called paraganglionomas or chemodectomas) are rare and usually present as painless neck masses. Most of these tumors are slow growing and benign, but lymph node metastases have been reported. If untreated, they are locally invasive; a large tumor may cause vagus or hypoglossal nerve deficit from mass effect or may encircle the internal carotid artery to the skull base. The tumor is hypervascular and splays the internal and external carotid arteries, giving it a classic angiographic appearance of a tumor blush in the center of a widened carotid bifurcation. Biopsy is contraindicated; diagnosis is made by CT angiography or MRA. Preoperative angiography for tumor embolization and test occlusion of the internal carotid artery may be considered for tumors over 4 cm in diameter. Using the same approach as for carotid endarterectomy, the tumor is resected from the carotid artery, with care to preserve the artery wall adventitia. Many small arteries arising from the external and internal carotid arteries supply the tumor and must be ligated individually. The incidence of cranial nerve injury with resection of large tumors approaches 40%. Prognosis after complete resection is excellent, with survival equal to that of age-matched controls and long-term recurrence of 6%.

Carotid Artery Aneurysms

Carotid aneurysms are much more common in the intracerebral than in the cervical portion of the carotid arteries. Most often, cervical aneurysms arise in the common carotid artery and are fusiform; these are associated with atherosclerosis. Traumatic aneurysms can be related to healing of an internal carotid dissection or to penetrating trauma. Mycotic aneurysms can be caused by staphylococcal, Escherichia coli, or tuberculous infections. Many other vasculitides are associated with carotid aneurysms, such as Behçet's disease, Takayasu's disease, fibromuscular dysplasia, and segmental arterial mediolysis. Anytime a mass in the neck is pulsatile, an aneurysm should be considered and diagnosis confirmed by angiography. Other symptoms include neck pain, cranial nerve dysfunction, and TIA or stroke. Surgery should be considered for aneurysms resulting from penetrating trauma, aneurysms associated with neurologic deficit, mycotic aneurysms, and aneurysms over 2 cm in diameter. Primary repair of the artery may be accomplished for most penetrating injuries. Carotid resection and interposition grafting are performed for most other aneurysms.

Assadian A et al: Long-term results of covered stent repair of internal carotid artery dissections. J Vasc Surg 2004;40:484.

Bergeron P et al: Long-term results of endovascular exclusion of extracranial internal carotid artery aneurysms and dissecting aneurysm. J Interv Cardiol 2004;17:245.

Luna-Ortiz K et al: Carotid body tumors: review of a 20-year experience. Oral Oncol 2005;41:56.

Thanvi B et al: Carotid and vertebral artery dissection syndromes. Postgrad Med J 2005;81:383.

Visceral Artery Insufficiency

Chronic intestinal ischemia results from atherosclerotic occlusive lesions at the origins of the superior mesenteric artery (SMA), celiac artery, and inferior mesenteric artery (IMA). Because of collateral flow via the middle colic artery branch of the SMA and the ascending colic artery of the IMA, the superior and inferior pancreaticoduodenal arteries, and the superior and inferior hemorrhoidal arteries, bowel ischemia does not occur until two of the three main visceral arteries are diseased severely. In fact, almost 30% of patients with peripheral vascular disease have asymptomatic occlusive disease of the mesenteric arteries. Symptoms consist of postprandial epigastric pain, and at later stages, food avoidance (sitophobia), resulting in weight loss. Chronic intestinal ischemia is a diagnosis of exclusion, derived after a negative workup for peptic ulcer disease, gastroesophageal reflux, pancreatitis, irritable bowel syndrome, and malignancy. A suggestive history in a person over 45 years of age who appears chronically ill, has risk factors for arterial occlusive disease, and has no other identifiable cause for abdominal symptoms is an indication for arteriography. Intravenous hydration must be provided to avoid acute bowel ischemia from catheter-induced or contrast-associated arterial spasm. Surgical or endovascular management is directed toward restoration of antegrade visceral arterial flow. Transaortic endarterectomy and mesenteric artery bypass are associated with a 5–9% mortality rate and a 10–25% recurrence rate at long-term follow-up. A higher recurrence rate is observed with stenting of short-segment lesions; these patients require

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routine angiographic follow-up. Survivors have an unexpectedly good long-term life expectancy.

Celiac axis compression syndrome (stenosis of the celiac artery caused by external compression of the arcuate ligament) has been described as a variant of chronic mesenteric ischemia. As an isolated entity, it is occasionally associated with cramping abdominal pain, nausea, vomiting, and diarrhea. Division of the arcuate ligament may be combined with celiac artery dilation. The pathophysiological basis for this disease remains elusive.

Acute intestinal ischemia may result from (1) embolic occlusion of a visceral branch of the abdominal aorta, generally in patients with mitral valvular disease, atrial fibrillation, or left ventricular mural thrombus; (2) thrombosis of an atherosclerotic mesenteric vessel; (3) low-flow or shock state due to cardiac failure or arterial spasm induced by ergot or cocaine intoxication; or (4) postcoarctectomy syndrome, producing nonocclusive mesenteric vascular insufficiency. Emboli are responsible for almost half of all cases. Symptoms include sudden onset of severe epigastric and periumbilical abdominal pain with minimal appreciable findings on abdominal examination (“pain out of proportion to physical findings”) and a high leukocyte count. Lactic acidosis, hypotension, and abdominal distention indicate bowel infarction. Mortality approaches 80% despite aggressive surgical management.

Visceral angiography can be performed in the stable patient; duplex ultrasound is of less diagnostic value in this setting. Mesenteric thrombosis causes occlusion at the origin of the vessel, while emboli most often lodge within the superior mesenteric artery usually at the first jejunal branch. In hypoperfusion-related mesenteric ischemia, the vessels are pruned but patent. Angiography also allows delivery of catheter-directed therapy: thrombolytics (alteplase, 0.5–1 mg/h) for thrombotic disease or vasodilators (papaverine, 30–60 mg/h) for nonocclusive disease. Broad-spectrum antibiotics are administered to all patients. Embolic disease, acidosis, hemodynamic instability, or severe or progressive abdominal pain mandate emergent laparotomy. Mesenteric flow is first reestablished with thromboembolectomy or bypass, and the bowel resection margins are then determined by gross inspection or examination with fluorescein. A second-look operation is planned if any bowel is of questionable viability at the close of the case.

Mesenteric vein occlusion is responsible for 5–15% of cases of acute mesenteric ischemia. Risk factors include hypercoagulable state (malignancy; protein C, protein S, or antithrombin III deficiency; presence of anticardiolipin or antiphospholipid antibody; polycythemia vera), intra-abdominal sepsis, previous splenectomy or portal angiography or sclerotherapy, portal hypertension, and cirrhosis. Diagnosis is made by contrast-enhanced abdominal CT scan or arterial portography. Patients should be treated with long-term anticoagulation. Surgery is reserved for those suspected of having bowel infarction and consists of bowel resection and occasionally venous thrombectomy. In some cases, percutaneous transhepatic administration of thrombolytics has been successful.

Ischemic colitis can develop as a result of acute or chronic colonic ischemia and is characterized by bouts of crampy lower abdominal pain and mild—often bloody—diarrhea. This picture may be indistinguishable from inflammatory bowel disease. Colonoscopy reveals segmental inflammatory changes, most prominent in the watershed areas of the rectosigmoid junction and splenic flexure. Conservative management is usually adequate. Surgery may be indicated for progressive symptoms or stricture formation.

Angelelli G et al: Acute bowel ischemia: CT findings. Eur J Radiol 2004;50:37.

Baixauli J et al: Investigation and management of ischemic colitis. Cleve Clin J Med 2003;70:920.

Brown DJ et al: Mesenteric stenting for chronic mesenteric ischemia. J Vasc Surg 2005;42:268.

Burns BJ et al: Intestinal ischemia. Gastroenterol Clin North Am 2003;32:1127.

Edwards MS et al: Acute occlusive mesenteric ischemia: surgical management and outcomes. Ann Vasc Surg 2003;17:72.

Oldenburg WA et al: Acute mesenteric ischemia: a clinical review. Arch Intern Med 2004;164:1054.

Renal Artery Stenosis

Renal artery stenosis is produced predominantly by atherosclerotic occlusive disease (80–90% of patients) or fibromuscular dysplasia (10–15% of patients). Characteristically, patients with occlusive disease have common risk factors for atherosclerosis, and their lesions are focal proximal or ostial calcific plaques, often described as “spillover” aortic disease. Patients with fibromuscular dysplasia tend to be women 30–50 years of age with distal renal artery disease that often extends into the branch vessels in a classic “string of beads” pattern of alternating stenoses and dilations.

Renal artery stenosis has two important clinical manifestations: renovascular hypertension and ischemic nephropathy. Renovascular hypertension accounts for about 5% of all cases of hypertension. In certain subsets of patients, the incidence is much higher. Seventy percent of patients over 60 years of age with diastolic blood pressure greater than 105 mm Hg and serum creatinine greater than 2 mg/dL have renovascular hypertension. In hypertensive children, the incidence of this disease approaches 80%. Evaluation should be considered in patients with poorly controlled or acutely worsening hypertension that was previously well controlled by drug therapy (three or more antihypertensive medications), particularly when renal insufficiency, lateral abdominal bruit, or noncardiogenic “flash” pulmonary edema present in conjunction. A history of acute renal failure when starting an angiotensin-converting enzyme inhibitor is highly suggestive.

An incidental finding of renal artery stenosis greater than 50% is noted in as many as 45% of patients

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undergoing angiography for aortoiliac occlusive disease. Infrequently, it is associated with progressive renal insufficiency. High-grade (over 70%) bilateral stenoses or stenosis in a solitary kidney warrant close follow-up. Renal artery occlusive disease is suspected in patients with rapidly progressive renal insufficiency and no evidence of obstructive uropathy or intrinsic renal disease (no proteinuria on urinalysis, no polycystic disease on ultrasound).

Initial screening tests include duplex ultrasound, captopril renal scintigraphy, and MRA. Sensitivity and specificity of detecting renal artery stenosis greater than 60% are over 90% for each of these modalities, but the tests are highly operator dependent and equipment dependent—the most reliable examination varies by institution. An assessment should also be made of the kidney parenchyma: renal length, cortical thickness, and presence of infarcts. One pitfall of these modalities is failure to identify small accessory renal arteries, which when diseased can contribute to renovascular hypertension.

Indications for treatment include renovascular hypertension refractory to aggressive drug therapy or renal artery stenosis with progressive renal failure or sudden-onset noncardiogenic pulmonary edema. Severe stenosis unaccompanied by renal insufficiency or poorly controlled hypertension may be considered for therapy to prevent loss of renal mass.

Angiography is generally required for planning an operative strategy and in many cases discloses a lesion amenable to angioplasty and stenting. Ideal lesions for endovascular treatment are focal, proximal, nonostial plaques that do not extend into the branch vessels. Primary stenting is advised for stenoses in renal arteries greater than 5 mm in diameter because of improved patency over angioplasty alone. One exception to this rule is fibromuscular dysplasia, in which a durable clinical effect is often produced by angioplasty alone. In patients with renal insufficiency, use of nonionized contrast, preprocedure intravenous hydration, and administration of the antioxidant acetylcysteine, 600 mg orally twice daily for 2 days before and 2 days after examination, are advised. The long-term patency of renal artery stents is yet undefined, but a 20% restenosis rate from intimal hyperplasia is noted at 6–36 months. Overall, 3–13% of initially stented patients ultimately require surgery.

Surgery is indicated for threatened loss of total renal mass (bilateral renal artery stenosis greater than 75%), for treatment of progressive renal failure or uncontrolled renovascular hypertension in patients with lesions refractory to angioplasty, for complex lesions extending into the branch vessels, or for concomitant aortic disease requiring surgical reconstruction. Because of superior long-term patency, surgery may be preferred over angioplasty for primary treatment of renal artery occlusive disease in good-risk younger surgical candidates. Surgical options include transaortic renal endarterectomy, renal artery bypass, or extra-anatomic (hepatorenal, splenorenal, or iliorenal) bypass. Mannitol (25 g intravenously) and fenoldopam (0.5–1 mcg/kg/min) have been beneficial in the perioperative management of these patients. Nephrectomy is considered for patients with renovascular hypertension and irreversible renal atrophy (kidney length less than 7 cm, severe cortical thinning, less than 10% of total renal function by split function testing). Endarterectomy and aortorenal bypass have 5-year patency greater than 80%, with beneficial blood pressure response in 70–90% of patients and improvement or stabilization in renal function in 70–80%.

Bax L et al: STAR Study Group: the benefit of Stent placement and blood pressure and lipid-lowering for the prevention of progression of renal dysfunction caused by Atherosclerotic ostial stenosis of the Renal artery. The STAR-study: rationale and study design. J Nephrol 2003;16:807.

Gill KS et al: Atherosclerotic renal arterial stenosis: clinical outcomes of stent placement for hypertension and renal failure. Radiology 2003;226:821.

Marekovic Z et al: Long-term outcome after surgical kidney revascularization for fibromuscular dysplasia and atherosclerotic renal artery stenosis. J Urol 2004;171:1043.

Olin JW: Renal artery disease: diagnosis and management. Mt Sinai J Med 2004;71:73.

Rao RK et al: Current endovascular management of atherosclerotic renal artery stenosis. Surg Clin North Am 2004;84: 1353.

Zhang H et al: Renal MR angiography. Magn Reson Imaging Clin North Am 2004;12:487.

Acute Limb Ischemia

Acute limb ischemia can be embolic, thrombotic, or traumatic. Symptoms and signs are related to the location of the occlusion, the duration of ischemia, and the degree of development of collateral circulation. Baseline pulse examination and assessment of motor and sensory function are imperative. Characteristically, acute ischemia is described by the six Ps: pain, pallor, pulselessness, paresthesias, poikilothermia, and paralysis. Pain and paresthesias are the most common early symptoms.

The following differential points should be considered: (1) Are there manifestations of advanced occlusive arterial disease in other areas, especially the opposite extremity (bruit, absent pulses, secondary skin changes), and is there a history of intermittent claudication? These findings suggest primary arterial thrombosis. (2) Is there a history of rheumatic heart disease, atrial fibrillation, or myocardial infarction? These findings suggest embolism.

1. Arterial Embolism

Eighty to 90 percent of arterial emboli arise from the heart. Atrial fibrillation is present in 60–70% of patients with arterial emboli and is associated with formation of thrombus in the left atrial appendage. Thrombus within a postinfarct ventricular aneurysm may also be a potential embolic source. Emboli arising from rheumatic heart disease are decreasing in incidence and now comprise less than 20% of arterial emboli. Cardiac valvular prostheses and cardiac tumors

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(myxomas) can also produce emboli. Noncardiac emboli arise from atherosclerotic lesions in proximal vessels, tumors, and foreign bodies. Paradoxic emboli deriving from deep venous thrombosis (DVT) in the leg can also occur.

Emboli tend to lodge at the bifurcation of major arteries, with 40% going to the aortic, femoral, or popliteal bifurcations. Thirty percent lodge in the cerebrovascular vessels, 10% in the visceral vessels, and 15% in the upper extremity vessels. Noncardiac emboli from arterial ulcerations are usually small (> 400 mcm), giving rise to peripheral ulceration and digital ischemia or occasionally to a systemic illness resembling vasculitis.

Treatment

Heparin sodium should be given as soon as the diagnosis of acute arterial occlusion is made and continued intraoperatively to prevent distal thrombosis. Emergent embolectomy is performed by introducing a balloon catheter through a small arteriotomy. An embolus at the aortic bifurcation or in the iliac artery can often be removed under local anesthesia through unilateral or bilateral common femoral arteriotomies. Smaller balloon catheters passed distally from the femoral artery can be used to extract popliteal or tibial emboli, though these often require popliteal arteriotomy. Percutaneous catheter techniques (aspiration, mechanical thrombolysis, or thrombolytic therapy) have some reported success in treatment of peripheral embolic disease. Lifelong anticoagulation is recommended because of the high frequency of recurrent emboli. Surface or TEE should be performed to exclude the possibility of atrial thrombus, valvular disease, or cardiac tumor.

Embolectomy performed more than 6 hours following onset of symptoms is often accompanied by development of a compartment syndrome. In mild cases, fasciotomy performed at the time of embolectomy can result in full functional recovery of the limb. The most common persistent major neurologic deficit is foot drop secondary to peroneal nerve ischemia. Myoglobinuria and renal failure can result from rhabdomyolysis and can be minimized with aggressive hydration, induced diuresis, and alkalinization of the urine. These measures decrease the risk of myoglobin precipitation in the renal tubules. One regimen involves initial infusion of 250 mL/h of crystalloid, half as 0.45 normal saline and the rest as D5W, with two ampules of sodium bicarbonate and 12.5 g of mannitol per liter of fluid taken if the diagnosis is delayed. Severe cases of compartment syndrome may result in anuric renal failure and systemic inflammatory response syndrome. In these patients, primary amputation may be lifesaving.

Prognosis

Arterial embolism is associated with a 5–25% risk of limb loss and a 25–30% in-hospital mortality. Heart disease is responsible for the majority of these deaths.

In patients with atrial fibrillation, mechanical or pharmacologic cardioversion or long-term anticoagulant therapy may decrease the risk of further emboli.

If no heart disease exists, prognosis is dependent on identification and exclusion of the embolic source. Cholesterol emboli from proximal arterial aneurysm or ulceration may occlude small distal vessels, producing digital ischemia. One common scenario is “blue toes” after aortography or aortic cross-clamping for coronary artery bypass or aneurysm repair. However, atheroemboli can also produce TIAs, acute renal insufficiency, or bowel ischemia depending on their location. Microhematuria, eosinophilia, and an elevated sedimentation rate are detectable transiently on laboratory testing. Biopsy of the infarcted tissue reveals cholesterol clefts in the small vessels under polarized light. These lesions are not treatable by embolectomy because the vessels involved are so small, and heparinization may worsen the problem by liberating more fragments from an ulcerated atherosclerotic plaque. Aortic or iliac lesions can be treated by endarterectomy, by resection and interposition graft, or by placement of a covered stent.

2. Acute Arterial Thrombosis

Acute arterial thrombosis is most commonly a complication of chronic atherosclerotic occlusive disease but can also occur as a consequence of trauma, low-flow states such as hypovolemic or cardiogenic shock, or an inflammatory arteritis. Polycythemia, dehydration, and hypercoagulable states also increase the risk of thrombosis. Generally, thrombus starts at the point of greatest stenosis and propagates distally to the next open branch point, such as a patent collateral vessel.

Treatment

Nonoperative treatment is the initial approach for many patients with acute arterial thrombosis. Because thrombosis develops in the setting of chronic occlusive disease, there are usually well-developed collaterals and little arterial spasm. The extremity is able to tolerate the longer periods of ischemia required for catheter-directed thrombolysis. Instillation of alteplase (0.5–1 mg/h) directly into the thrombus through a multiside-holed catheter may allow recanalization of distal vessels that are less amenable to surgical thrombectomy. It also helps disclose the underlying stenotic lesion, which can then be treated with angioplasty, endarterectomy, or bypass grafting. Thrombolysis is successful in 50–80% of cases, with a limb salvage rate approaching 90%.

Less commonly, arterial thrombosis follows penetrating trauma, such as arterial transection and foreign body embolization, or blunt trauma, such as posterior knee dislocation and crush injury. These patients require surgical treatment. The vessel involved may be previously undiseased, with only a few small collaterals. Thrombolysis is generally not indicated because of

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the more advanced state of limb ischemia on presentation and the high incidence of bleeding complications.

Prognosis

Limb salvage is usually possible with acute thrombosis of the iliac or superficial femoral arteries but is less likely with popliteal thrombosis because of the paucity of available collaterals. Acute thrombosis of a popliteal aneurysm is associated with a 10–25% risk of amputation.

Clagett GP et al: Antithrombotic therapy in peripheral arterial occlusive disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3 Suppl):609S.

Earnshaw JJ et al: National Audit of Thrombolysis for Acute Leg Ischemia (NATALI): clinical factors associated with early outcome. J Vasc Surg 2004;39:1018.

Kessel DO et al: Infusion techniques for peripheral arterial thrombolysis. Cochrane Database Syst Rev 2004;(1): CD000985.

Other Arteriopathies

Thromboangiitis Obliterans (Buerger's Disease)

Buerger's disease is an episodic and segmental inflammatory and thrombotic process of the peripheral arteries and veins. The cause is not known. It is seen most commonly in men under 40 years of age who smoke, and particularly in those of Eastern European or Asian background. It is characterized by occlusion of distal arteries, producing claudication, rest pain, and tissue necrosis. The inflammatory process is intermittent, with quiescent periods lasting weeks, months, or years. Different arterial segments may become occluded in successive episodes; recanalization can occur during periods of disease remission.

There are no pathognomonic signs, but several findings are characteristic of Buerger's disease. (1) The typical patient is a man under 40 years of age who smokes. Fewer than 20% of patients are women. (2) There is a history of migratory superficial segmental thrombophlebitis, eg, red, tender nodules in the branches of the saphenous vein. Biopsy of the affected vein may show inflammatory infiltrate in the vessel wall, microabscesses, and thrombus or recanalization with perivascular fibrosis, depending on the stage of disease. (3) Intermittent claudication typically begins in the arch of the foot and progresses to the calf; instep claudication is not typical of atherosclerotic occlusive disease. Rest pain and diminished sensation from ischemic neuropathy are present in over 70% of patients at presentation. (4) Proximal pulses are normal, whereas distal pulses are absent. Digital disease is often asymmetric: Not all of the toes are affected to the same degree. The affected digits may be pale, cyanotic, erythematous, or gangrenous. (5) Ulcers are present in 75% of patients and are typically located at the nail margins. (6) The disease is never confined to one limb. Although not all limbs may be symptomatic, an abnormal Allen test or distal pulse examination can usually be demonstrated. (7) There is often a history of cold sensitivity or Raynaud's phenomenon. (8) The clinical course is usually episodic, with acute exacerbations followed by rather definite remissions. By contrast, steadily progressive symptoms are typical in atherosclerotic occlusive disease.

Atherosclerotic occlusive disease, emboli, and autoimmune disorders are included in the differential diagnosis. Several angiographic findings can be helpful in making these distinctions. Buerger's disease involves the distal arteries and spares the proximal arteries; it is segmental in appearance, with skip areas of disease; there is no vascular calcification; and extensive collateralization via tortuous “corkscrew” vessels is typical. Peripheral ultrasound or angiography and echocardiography are helpful in excluding an embolic source. Blood tests (complete blood count, coagulation studies, sedimentation rate, antinuclear antibody, lupus anticoagulant, rheumatoid factor, anticentromere antibody, and antiphospholipid antibody) are obtained to rule out vasculitis, lupus erythematosus, scleroderma, rheumatoid vascular disease, or a hypercoagulable state due to antiphospholipid antibody syndrome. A careful history is generally sufficient to exclude other rare disorders that may mimic Buerger's disease, such as ergotamine intoxication, cannabis arteritis, or small vessel occlusive disease secondary to the use of vibratory tools (hypothenar hammer syndrome).

Smoking cessation is imperative. The disease can remain active with as little as a single cigarette a day; chewing tobacco, marijuana, nicotine patches, nicotine gum, and exposure to second-hand smoke must all be eliminated to arrest the disease process. Local wound care of ulcers consists of limited debridement, appropriate dressings, and intravenous antibiotics for cellulitis. Nonulcerated skin should be kept moisturized. Lamb's wool between the toes and heel protectors or sheepskin-lined boots (Rooke boots) help reduce further trauma to the skin. Warming pads must be used judiciously, as burns are possible in patients with diminished sensation from peripheral neuropathy. Supplementary oxygen by nasal cannula is often used to increase oxygen supply to the wound. Some ulcers may respond to hyperbaric oxygen.

Nonsteroidal anti-inflammatory medications and opioids are used for pain control. Aspirin (81 mg daily) or another antiplatelet agent is generally prescribed to reduce thrombotic complications. Calcium channel blockers are often used to promote vasodilation. Preliminary trials have shown intravenous infusion of the prostaglandin analog iloprost to be efficacious in healing of ischemic ulcers, but the drug is not yet available in the United States. Vascular endothelial growth factor (VEGF) is also being investigated for use in Buerger's disease.

Rarely do distal target vessels exist for arterial bypass. Sympathectomy may at least transiently reduce

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the vasospastic manifestations of the disease and aid in the establishment of collateral circulation to the skin. It is indicated for relief of intractable rest pain and healing of ulcers refractory to other treatment. Sympathectomy is often performed in conjunction with digital amputation. Amputation is reserved for patients with wet gangrene or severe rest pain.

Prognosis depends on the success of smoking cessation. Over 90% of patients who quit smoking avoid further amputation.

Calguneri M et al: Buerger's disease with multisystem involvement. A case report and a review of the literature. Angiology 2004;55:325.

Ohta T et al: Clinical and social consequences of Buerger disease. J Vasc Surg 2004;39:176.

Olin JW: Current concepts: thromboangiitis obliterans (Buerger's disease). N Engl J Med 2000;343:864.

Idiopathic Arteritis of Takayasu (“Pulseless Disease”)

Takayasu's disease is a rare polyarteritis of unknown cause with a special predilection for the branches of the aortic arch. It results in segmental stenoses, occlusions, and aneurysms. It is seen frequently in Asian women under the age of 40 years. There are a myriad of clinical presentations depending on the stage of disease (early “inflammatory” or late “occlusive”) and the arteries involved. Early stages of disease are often accompanied by fever, myalgias, arthralgias, and pain over the involved artery as well as leukocytosis and elevated sedimentation rate. Other symptoms are related to arterial insufficiency: syncope, dizziness, amaurosis fugax, stroke, angina, pulmonary hypertension, and claudication. Hypertension related to proximal renal artery stenosis or aortic coarctation is present in over 25% of patients. Vascular bruits, diminished peripheral pulses, or asymmetric blood pressure measurements are common findings on physical examination.

Angiography is essential for diagnosis and most often will reveal combined occlusive and aneurysmal disease. The most commonly involved vessels are the subclavian artery, descending thoracic aorta, renal artery, carotid artery, and mesenteric arteries, although the ascending and abdominal aorta and the vertebral, coronary, pulmonary, iliac, and brachial arteries can also be affected. In cases of upper extremity stenoses, aortic root pressure should be measured by manometry at the time of angiography to assess for essential hypertension. MRA can also be used for routine surveillance of patients with suspected Takayasu's disease.

Pulseless disease must be differentiated from vascular lesions of the aortic arch due to atherosclerosis, though in the latter instance concomitant lower extremity disease is invariably present. Histologically, the arterial lesions are indistinguishable from those of giant cell arteritis. In the early, active stage, corticosteroids (prednisone, 1 mg/kg/d) are used to control symptoms and limit the progression of disease; cytotoxic agents may be added if corticosteroids are ineffectual. Surgical or percutaneous intervention is not advised until the disease becomes indolent. Bypass of the occluded or aneurysmal segments is the usual surgical approach. Histologic examination of the resected artery may show nonspecific transmural inflammation or chronic fibrosis. Percutaneous angioplasty or stenting is possible for short-segment stenoses, but there is a high recurrence rate in these usually noncompliant vessels.

Kissin EY et al: Diagnostic imaging in Takayasu arteritis. Curr Opin Rheumatol 2004;16:31.

Liang P et al: Takayasu's arteritis: vascular interventions and outcomes. J Rheumatol 2004;31:102.

Vanoli M et al; Itaka Study Group: Takayasu's arteritis: A study of 104 Italian patients. Arthritis Rheum 2005;53:100.

Fibromuscular Dysplasia

Fibromuscular dysplasia is a nonatherosclerotic, noninflammatory disease of unknown cause characterized by segmental irregularity of small and medium-sized muscular arteries. Typically, it affects white women 30–50 years of age; a family history of disease is not unusual. The most frequently involved vessels (in descending order) are the renal, carotid, and common iliac arteries. Fibromuscular dysplasia presents with renovascular hypertension and, less often, with renal insufficiency, TIAs, or claudication. Angiography reveals a “string of beads” pattern of disease. There are four recognized histologic types of fibromuscular dysplasia: medial fibrodysplasia, intimal fibroplasia, medial hyperplasia, and perimedial dysplasia, though the first type is responsible for over 80% of all cases. Aspirin is advised for most patients. Percutaneous or surgical intervention is reserved for symptomatic patients. Most lesions respond well to percutaneous angioplasty; stents do not appear to offer any advantage over angioplasty alone. More complex lesions extending into branch vessels may require interposition grafting. It is important to recognize that intracranial aneurysms are present in up to 50% of patients with internal carotid fibromuscular dysplasia.

Birrer M: Treatment of renal artery fibromuscular dysplasia with balloon angioplasty: a prospective follow-up study. Eur J Vasc Endovasc Surg 2002;23:146.

Guill CK et al: Fatal mesenteric fibromuscular dysplasia: a case report and review of the literature. Arch Intern Med 2004; 164:1148.

Olin JW: Renal artery disease: diagnosis and management. Mt Sinai J Med 2004;71:73.

Vasculitis

The term vasculitis describes a diverse group of inflammatory disorders characterized by multiorgan system vascular involvement, systemic markers of disease (fever, malaise, weight loss, elevated white blood cell count and

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sedimentation rate), and suspected immunologic origin. Often there are accompanying rheumatologic or cutaneous manifestations such as arthralgias, conjunctivitis, or erythema nodosum. Drugs (amphetamines, cocaine, hydralazine, procainamide), infections (hepatitis B, gonococcus, streptococcus), chronic inflammatory diseases, and cancer are cited as inciting causes for vasculitis. These diseases can be grouped into disorders that affect medium and large blood vessels (polyarteritis nodosa, scleroderma, systemic lupus erythematosus, temporal arteritis, Behçet's disease, Kawasaki syndrome, rheumatoid arteritis, relapsing polychondritis) and those that affect smaller vessels (Churg-Strauss syndrome, Wegener's granulomatosis, Henoch-Schönlein purpura, essential mixed cryoglobulinemia). These are discussed in detail in Chapter 20. In general, the vascular lesions are treated with anti-inflammatory medications. Surgery is indicated for acute complications (bowel infarction, gangrene, or aneurysm rupture) and for chronic ischemic symptoms or large aneurysms in patients with quiescent disease.

Vasomotor Disorders

Raynaud's Disease & Raynaud's Phenomenon

Essentials of Diagnosis

  • Episodic bilateral digital pallor, cyanosis, and rubor.

  • Precipitated by cold or emotional stress; relieved by warmth.

  • Seventy to 80 percent of patients are women.

General Considerations

Raynaud's syndrome is an episodic vasospastic disorder characterized by digital color change (white-blue-red) with exposure to cold environment or emotional stress. If idiopathic, it is called Raynaud's disease. If associated with a possible precipitating systemic or regional disorder (autoimmune diseases, myeloproliferative disorders, multiple myeloma, cryoglobulinemia, myxedema, macroglobulinemia, or arterial occlusive disease), it is called Raynaud's phenomenon. The incidence of disease is estimated to be as high as 10% in the general population. Other vasospastic disorders, such as variant angina and migraine headache, are common in patients with Raynaud's syndrome. An abnormality of the sympathetic nervous system has long been implicated in the etiology of Raynaud's disease; recently, research has focused on the theory of up-regulation of vascular smooth muscle α2-adrenergic receptors.

Clinical Findings

Classically, Raynaud's disease and Raynaud's phenomenon are characterized by intermittent attacks of pallor of the hands or fingers brought on by cold or emotional stress, progressing to cyanosis and then rubor on rewarming. Mild discomfort, paresthesias, numbness, and trace edema often accompany the color changes. In Raynaud's disease, the disease is symmetric, by rule; in Raynaud's phenomenon, the changes may be most noticeable in one hand or even in one or two fingers only. Infrequently, the feet and toes are involved. Between attacks, the affected extremities may be entirely normal.

The distinction between Raynaud's disease and Raynaud's phenomenon is meant to reflect a difference in prognosis. Whereas Raynaud's disease is benign and often controllable, Raynaud's phenomenon may progress to atrophy of the terminal fat pads and development of fingertip gangrene. However, because many inciting diseases may not be clinically suspected at the time the diagnosis of Raynaud's disease is made, there is a large degree of crossover between groups. The diagnosis is based on clinical criteria. Raynaud's disease appears first between ages 15 and 45, almost always in women. A patient with suggestive symptoms that persist for over 3 years without evidence of an associated disease is given the diagnosis of Raynaud's disease.

Differential Diagnosis

A patient with Raynaud's syndrome must be evaluated for possible inciting systemic disorders. Directed history and physical examination and serologic testing may be helpful in excluding the collagen-vascular disorders, which include scleroderma, systemic lupus erythematosus, dermatomyositis, and rheumatoid arthritis. It is estimated that Raynaud's phenomenon ultimately develops in 80% of patients with scleroderma. Likewise, cryoglobulinemia can be excluded by appropriate testing. Raynaud's phenomenon is also occasionally seen in patients with neurogenic thoracic outlet syndrome or carpal tunnel syndrome. Frostbite, ergotamine toxicity, and use of chemotherapeutic agents, which can also be associated with Raynaud's phenomenon, can usually be excluded by a careful history; symptomatic vasospastic disease develops in up to one-third of patients receiving combined bleomycin and vincristine (such as for testicular cancer). An abnormal or asymmetric pulse examination, differential blood pressure cuff measurements, gangrene, or a positive Allen test are suggestive of arterial occlusive disease and should prompt upper extremity angiography to exclude stenosis or occlusion from atherosclerosis, Buerger's disease, arterial thoracic outlet syndrome, embolic disease, or repetitive motion injury of the small vessels of the hand. Even undiseased upper extremity vessels often show intense vasospasm with contrast injection, so the arm is wrapped for warmth and prophylactic use of a vasodilator (papaverine or nitroglycerin,

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30 mg, injected through the angiography catheter) is advised; both arms are imaged for side-by-side comparison.

Other vasospastic disorders that should be included in the differential but are usually easily distinguishable by physical examination are acrocyanosis and livedo reticularis.

Treatment

A. General Measures

Warmth and protection of the hands are the basic tenets of therapy. In Raynaud's phenomenon, wounds heal slowly, and infections are consequently hard to control. Gloves should be worn in cold environments and during activities that may cause trauma to the skin, such as dishwashing, gardening, woodworking, or office filing. Moisturizing lotion should be applied frequently to avoid fissured dry skin. Smoking cessation is imperative, as nicotine is a known vasoconstrictor. Stress management should be addressed when appropriate. Oral contraceptives, β-blockers, and ergotamines are associated with exacerbation of symptoms and ideally should be discontinued. Aspirin is prescribed to decrease the risk of thrombotic complications.

B. Vasodilators

Vasodilator drugs may be of some benefit in patients whose symptoms are not adequately controlled with simpler measures. Low-dose nifedipine (sustained release, 30 mg/d) or diltiazem (sustained release, 30 mg/d) has superseded topical or oral nitroglycerin for treatment of vasospasm. Use of prostaglandins has been disappointing, but the serotonin reuptake inhibitor and antidepressant fluoxetine (20 mg daily) shows some promise in reduction of the frequency and severity of attacks.

C. Surgery

Sympathectomy is indicated for pure vasospastic disease refractory to medical management. In the lower extremity, sympathectomy may produce complete and permanent relief of symptoms; however, for unclear reasons, the beneficial effects are often transient in the upper extremity. Limited improvement is seen in advanced ischemia, particularly if significant digital artery obstructive disease is present.

Prognosis

Raynaud's disease is usually benign, causing mild discomfort on exposure to cold and progressing very slightly over the years. The prognosis of Raynaud's phenomenon is that of the associated disease.

Grader-Beck T et al: Raynaud's phenomenon in mixed connective tissue disease. Rheum Dis Clin North Am 2005;31: 465.

Thompson AE et al: Calcium channel blockers for primary Raynaud's phenomenon: a meta-analysis. Rheumatology (Oxford) 2005;44:145.

Livedo Reticularis

Livedo reticularis is a vasospastic disorder of unknown cause that results in a painless, mottled discoloration on large areas of the extremities, generally in a fishnet pattern with reticulated cyanotic areas surrounding a paler central core. It occurs in men and women of all ages. In most instances, livedo reticularis is entirely benign; infrequently, it is associated with an occult malignancy, polyarteritis nodosa, atherosclerotic microemboli, or antiphospholipid antibody syndrome. The disorder is characterized by arteriolar vasoconstriction with capillary and venous dilation; the particular pattern is believed to represent arborization of capillaries surrounding the feeding arteriole.

Livedo reticularis is most apparent on the thighs but can occur on the forearms or lower abdomen and is most pronounced in cold weather. In warm environments, the reticular pattern may fade but does not entirely disappear. A few patients report paresthesias, coldness, or numbness in the involved areas. Peripheral pulses are normal. The affected regions may be cool. Skin ulceration is rare. Treatment consists of protection from exposure to cold; use of vasodilators is seldom indicated. In the rare patient in whom ulcerations or gangrene develops, an underlying systemic disease should be excluded.

Acrocyanosis

Acrocyanosis is an uncommon vasospastic disorder characterized by persistent cyanosis of the hands and feet and, to a lesser degree, the forearms and legs. It is associated with arteriolar vasoconstriction combined with dilation of the subcapillary venous plexus of the skin, through which deoxygenated blood slowly circulates. It is worse in cold weather but does not completely disappear during the warm season. It occurs primarily in women, is most common in the teens and twenties, and may improve with advancing age or during pregnancy. It is characterized by symmetric coldness, sweating, slight edema, and cyanotic discoloration of the hands or feet. Peripheral pulses are normal, and pain, trophic lesions, and disability do not occur.

Erythromelalgia

Erythromelalgia is a paroxysmal bilateral vasodilatory disorder of unknown cause. Idiopathic (primary) erythromelalgia occurs in otherwise healthy persons and affects men and women equally. A secondary type is occasionally seen in patients with polycythemia vera, hypertension, gout, and neurologic diseases.

The primary symptoms are erythema, warmth, and bilateral burning pain that lasts minutes to hours, at first involving circumscribed areas on the balls of the feet or palms and often progressing to involve the entire extremity. Symptoms occur in response to vasodilation produced by exercise or heat and can be prominent at night when the extremities are warmed under

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bedclothes. Relief may be obtained by cooling and elevating the affected extremity.

No findings are generally present between attacks. With onset of an attack, skin temperature and arterial pulsations are increased and the involved areas are warm, erythematous, and sweaty.

In primary erythromelalgia, aspirin (650 mg every 4–6 hours) often provides excellent relief and may in fact be diagnostic. Warm environments are to be avoided. β-Blockers, epidural corticosteroid injections, and lidocaine patches have reported anecdotal success. Secondary erythromelalgia may improve with treatment of the primary disease process.

Orstavik K et al: Pain in primary erythromelalgia—a neuropathic component? Pain 2004;110:531.

Waxman SG et al: Erythromelalgia: a hereditary pain syndrome enters the molecular era. Ann Neurol 2005;57:785.

Complex Regional Pain Syndrome Type 1 (Reflex Sympathetic Dystrophy)

Essentials of Diagnosis

  • Burning or aching pain of greater severity and longer duration than expected following trauma to an extremity.

  • Manifestations of localized vasomotor instability are generally present.

General Considerations

The syndrome is characterized by burning or aching pain in an injured extremity that is more severe than would be expected given the inciting trauma. It occurs in all age groups and equally in both sexes and can involve either the arms or the legs. The degree of trauma is in some cases surprisingly minor (phlebotomy), but most cases follow crushing injuries with lacerations and soft tissue destruction. Closed fractures, simple lacerations, burns (especially electric burns), elective operative procedures, and myocardial infarction with referred left arm pain are other reported causes.

Clinical Findings

In the early stages, the pain, tenderness, and hyperesthesia are localized to the injured area, and the extremity is warm, dry, swollen, and red or slightly cyanotic. With time, muscle spasm and joint stiffness limit mobility, and the nails may become ridged. In advanced stages, the pain is more diffuse, and nocturnal pain may become extreme; the extremity becomes cool and clammy and intolerant of temperature changes (particularly cold); and the skin becomes glossy and atrophic. The patient's dominant concern is to avoid external stimuli, particularly in trigger point areas. Pain and disuse lead to loss of function. Radiographs reveal asymmetric osteopenia more severe than anticipated from immobility alone.

Prevention

Trauma to peripheral nerves during surgery is avoided by knowledge of their anatomy and careful mobilization by handling of the perineural tissue only. Splinting and adequate analgesia followed by early mobilization of an injured extremity minimize the occurrence of reflex sympathetic dystrophy.

Treatment & Prognosis

A. Conservative Measures

Early recognition and treatment are essential to preserve function of the limb. In the early stages, when major secondary changes have not yet developed, physical therapy involving active and passive exercises combined with a mild anxiolytic (diazepam, 2 mg twice daily, or alprazolam, 0.125–0.25 mg twice daily) may relieve symptoms. Opioids have been a mainstay of treatment; recently, however, gabapentin (beginning at 200–900 mg twice daily) has been used with success. Sympathetic blocks (stellate ganglion or lumbar) can be combined with intensive physical therapy for cases refractory to more conservative treatment. Protection from further injury and avoidance of irritating stimuli are imperative.

B. Surgery

Patients who achieve significant temporary relief of symptoms after sympathetic blocks may be cured by sympathectomy. With advanced disease and in cases with significant psychological overlay, however, the prognosis for improvement with sympathectomy is poor. Implantable spinal cord biostimulator devices have had limited success.

Quisel A et al: Complex regional pain syndrome: which treatments show promise? J Fam Pract 2005;54:599.

Teasdall RD et al: Complex regional pain syndrome (reflex sympathetic dystrophy). Clin Sports Med 2004;23:145.

Thoracic Outlet Syndrome

Thoracic outlet syndrome can be subdivided into neurogenic, venous, and arterial types depending on which structures are compressed in the interscalene triangle or costoclavicular space.

Neurogenic thoracic outlet syndrome is the most common (over 90% of patients) and often the most difficult to diagnose and treat effectively. Patients most often present with supraclavicular and anterior chest pain often burning in nature and with segmental pain and paresthesias of the arm and hand in an ulnar

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nerve distribution. Weakness and atrophy of the forearm and of the intrinsic muscles of the hand secondary to disease are not uncommon. Thenar or hypothenar muscle wasting is rare. There is usually a history of whiplash trauma (motor vehicle accident, fall, assault) or repetitive activity of the upper extremity (word processing, filing), particularly overhead activities (lifting). Physical examination will often disclose supraclavicular tenderness and positive brachial plexus tension testing. A positive Adson test (obliteration of the radial pulse on inspiration while turning the head away from the affected side), or a positive Roos test (reproduction of symptoms with rapid opening and closing of the hand with the arm 90 degrees abducted at the shoulder and 90 degrees flexed at the elbow), or a positive Tinel sign (tingling in the distribution of the nerve produced by tapping in the supraclavicular interscalene region) may also be elicited. Presence of a cervical rib or other bony anomalies should be excluded by chest radiograph. Electrophysiologic testing is usually negative. The cornerstone of treatment is specific physical therapy such as the Edgelow Neurovascular Entrapment Self-Treatment (ENVEST) program, beginning with breathing exercises and attention to posture. Transcutaneous electrical nerve stimulation (TENS) can be helpful. Surgery is indicated in severe refractory cases and involves resection of the hypertrophied anterior and middle scalene muscles, brachial plexus neurolysis, and resection of muscular or fibrous bands and any bony abnormalities. Although in carefully selected patients the initial surgical outcome is excellent, symptoms return within a year in as many as 25% of patients, presumably due to late postoperative scarring around the nerve roots.

Venous thoracic outlet syndrome involves external compression of the subclavian vein by the first rib, anterior scalene muscle, clavicle, and costocoracoid ligament. A history of repetitive upper arm exercises or clavicular fracture is common. Positional venography is essential in the diagnosis of venous thoracic outlet syndrome; external compression of the vein and filling of venous collaterals are demonstrated by abduction of the arm. Thrombosis of the involved vein segment is known as Paget-Schroetter syndrome, or effort thrombosis, and often presents as acute unilateral arm edema, axillary fullness, hand cyanosis, and enlarged shoulder and chest wall collateral veins in an otherwise healthy patient. Evaluation for hypercoagulable state, including plasma levels of antithrombin III, factor V Leiden, cardiolipin antibody, and proteins C and S, is recommended, as an abnormality can be detected in some patients presenting with acute axillary-subclavian vein thrombosis. Treatment for symptomatic venous thoracic outlet syndrome involves anterior and middle scalenectomy and first rib resection with venolysis, which can be performed through a supraclavicular, a combined supraclavicular and infraclavicular, or a transaxillary approach. Intraoperative venography confirms relief of extrinsic compression. Residual stenosis can be dilated. If the vein is thrombosed, multimodality therapy is used: preoperative thrombolysis followed immediately by surgery with intraoperative angioplasty of any residual venous stenosis. If the vein cannot be recannulated preoperatively, surgical thrombectomy may be required. The prognosis is excellent with appropriate treatment.

Arterial thoracic outlet syndrome is the least common of these disorders and involves compression of the subclavian artery between the anterior and middle scalene muscles. It most often produces subclavian artery stenosis and poststenotic dilation, which result in digital ischemia due to atheroemboli. These lesions can be subtle, often requiring magnified multiplanar views to be shown angiographically. Arm claudication is a less common presentation. The Wylie-Allen test (performed by exsanguinating the arm with elevation, occluding the radial and ulnar arteries at the wrist, and observing capillary refill of the hand when these arteries are released) may reveal occult digital artery occlusions that can be confirmed by angiography. Treatment involves removal of the anterior and middle scalene muscles, first rib resection, and resection of the affected subclavian artery with replacement by a polytetrafluoroethylene interposition graft.

Crosby CA et al: Conservative treatment for thoracic outlet syndrome. Hand Clin 2004;20:43.

Sanders RJ et al: Venous thoracic outlet syndrome. Hand Clin 2004;20:113.

Schneider DB et al: Combination treatment of venous thoracic outlet syndrome: open surgical decompression and intraoperative angioplasty. J Vasc Surg 2004;40:599.

Venous Diseases

Varicose Veins

Essentials of Diagnosis

  • Dilated, tortuous superficial veins in the lower extremities.

  • May be asymptomatic or associated with fatigue, aching discomfort, bleeding, or localized pain.

  • Edema, pigmentation, and ulceration suggest concomitant venous stasis disease.

  • Increased frequency after pregnancy.

General Considerations

Abnormally dilated veins develop in several locations, giving rise to varicoceles, esophageal varices, and hemorrhoids. However, varicose veins are most commonly

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found in the legs as abnormally dilated, elongated, and tortuous alterations in the saphenous veins and their tributaries. Saphenous vein varicosities develop in 15% of adults. Risk factors include female gender, pregnancy, family history, prolonged standing, and history of phlebitis.

The long saphenous vein and its tributaries are most commonly involved, but the short saphenous vein may also be affected. These vessels lie immediately beneath the skin and superficial to the deep fascia.

An inherited vein wall or valvular defect appears to play a role in the development of most primary varicosities. Secondary varicosities may result from valve damage following thrombophlebitis, trauma, DVT, arteriovenous fistula, or nontraumatic proximal venous obstruction (pregnancy, pelvic tumor). Venous reflux caused by valvular incompetence is characteristic of both primary and secondary varicose veins. At the saphenofemoral junction and the perforating veins of the medial calf and thigh, the superficial and deep veins of the leg communicate; valve incompetence in these segments permits blood flow to be bidirectional. Thus, high venous pressures (> 300 mm Hg) from within the deep system that occur during calf compression associated with walking are transmitted to these superficial veins, which dilate. With long-standing disease, the surrounding tissue and skin may develop secondary changes such as fibrosis, chronic edema, and skin pigmentation and atrophy.

Clinical Findings

A. Symptoms

The severity of the symptoms is not necessarily correlated with the number and size of the varicosities. Dull, aching heaviness or a feeling of fatigue brought on by periods of standing is the most common complaint. Itching from an associated eczematoid dermatitis may occur above the ankle.

B. Signs

Dilated, tortuous, elongated veins on the medial aspect of the thigh and leg are usually readily visible with the patient standing. Smaller, flat, blue-green reticular veins, telangiectasias, and spider veins may accompany varicose veins and are further evidence of venous dysfunction. Secondary tissue changes may be absent even in the presence of extensive large varicosities; however, with superficial or deep venous insufficiency and long-standing varicose veins, the signs of chronic venous insufficiency appear. These may include brownish pigmentation and thinning of the skin above the ankle, edema, fibrosis, scaling dermatitis, and venous ulceration. Duplex ultrasonography is used to detect the precise location of incompetent valves. The Brodie-Trendelenburg test can help differentiate saphenofemoral valve incompetence from perforator vein incompetence. With the patient lying supine, the leg is elevated until all varicosities collapse. A tourniquet is placed at the mid thigh to exclude reflux secondary to incompetence at the saphenofemoral junction. With the tourniquet in place, the patient is asked to stand. Varicosities that remain collapsed indicate valvular insufficiency at the saphenofemoral junction. However, if the varicosities rapidly refill, perforator vein incompetence is implicated. The tourniquet can then be moved more distally to identify the location of the incompetent perforator.

Differential Diagnosis

Primary varicose veins should be differentiated from secondary varicose veins to exclude the possibility of chronic venous insufficiency of the superficial or deep system of veins, obstruction of the pelvic veins, arteriovenous fistula (congenital or acquired), or congenital venous malformation. If extensive varicose veins are encountered in a young patient—especially if unilateral and in an atypical distribution (lateral leg)—Klippel-Trénaunay syndrome must be considered. The classic triad of Klippel-Trénaunay syndrome is varicose veins, limb hypertrophy, and a cutaneous birthmark (port wine stain or venous malformation). Because the deep veins are often anomalous or absent, saphenous vein stripping is contraindicated. Standard treatment for patients with Klippel-Trénaunay syndrome is graduated support stockings and surgery for correction of leg length discrepancy.

Pain or discomfort secondary to arthritis, radiculopathy, or arterial insufficiency should be distinguished from symptoms associated with coexistent varicose veins.

Complications

Complications of varicose veins include secondary ulceration, bleeding, chronic stasis dermatitis, superficial venous thrombosis, and thrombophlebitis.

Treatment

A. Nonsurgical Measures

Knee-high or thigh-high elastic graduated compression stockings give external support to the superficial veins. For most patients, a gradient of compression of 20–30 mm Hg is appropriate. The stockings are worn all day to reduce venous hypertension due to pooling of blood and are removed at night. Periodic leg elevation and regular exercise are encouraged. In many patients, this program may provide relief of symptoms and discourage progression of disease sufficient to avoid surgery.

Small venous ulcers generally heal with leg elevation and compression bandages (Ace wrap or Unna boot). Varicose vein excision should be postponed until infection and edema are controlled.

B. Surgical Measures

Indications for surgical treatment include persistent or disabling pain, recurrent superficial thrombophlebitis, erosion of the overlying skin with bleeding, and manifestations of chronic venous insufficiency (particularly ulceration).

The operative plan is dependent on determination of the competency of the superficial, deep, or perforating

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veins and the location of sites of venous reflux. Preoperative duplex ultrasound is essential in the identification of incompetent perforating veins and in the assessment of the saphenofemoral junction. Surgery can then be tailored to the pattern of disease. Stab avulsion surgery is combined with prevention of reflux by high ligation of the saphenofemoral junction or ligation of perforator branches. Endovenous radiofrequency ablation of the proximal saphenous vein alone or combined with stab avulsion of calf varicosities is more frequently being used. Stripping of the entire saphenous system is rarely required and may be complicated by hematoma formation, infection, and saphenous nerve irritation.

C. Compression Sclerotherapy

Compression sclerotherapy can be used for telangiectasias, spider veins, and small (< 4 mm) varicosities that persist after vein stripping. With patients in a supine position, small volumes of a sclerosing solution (23.4% hypertonic saline or 2.5% sodium morrhuate) are injected, and direct pressure is then maintained with compression stockings. The goal is to obliterate the abnormal vein by inducing localized endothelial destruction and fibrosis. More than one treatment is often required. Complications—including allergic reactions, thrombophlebitis, neoangiogenesis, skin necrosis, or hyperpigmentation—are rare.

Prognosis

With careful patient selection and properly selected operative techniques, most patients experience relief of symptoms, and the recurrence rate is about 10%. Patients should be informed that this is a chronic disease and that prevention of new varicosities is dependent on continued use of the compression stockings, leg elevation, and exercise. If extensive varicosities reappear after surgery, the completeness of the high ligation should be questioned, and reexploration of the saphenofemoral area may be necessary. Even after adequate treatment, secondary tissue changes may not regress.

Kahle B et al: Efficacy of sclerotherapy in varicose veins—prospective, blinded, placebo-controlled study. Dermatol Surg 2004;30:723.

Lurie F et al: Prospective randomized study of endovenous radiofrequency obliteration (closure procedure) versus ligation and stripping in a selected patient population (EVOLVeS Study). J Vasc Surg 2003;38:207.

Mundy L et al: Systematic review of endovenous laser treatment for varicose veins. Br J Surg 2005;92:1189.

Thrombophlebitis of the Deep Veins

Essentials of Diagnosis

  • Pain in the calf or thigh, often associated with edema. Fifty percent of patients are asymptomatic.

  • History of congestive heart failure, recent surgery, trauma, neoplasia, oral contraceptive use, or prolonged inactivity.

  • Physical signs unreliable.

  • Duplex ultrasound is diagnostic.

General Considerations

Acute DVT affects as many as 800,000 new patients per year. Treatment of this disease is estimated to cost $1–2.5 billion per year, not including costs associated with long-term sequelae.

Although the cause is often multifactorial, Virchow's triad (stasis, vascular injury, and hypercoagulability) defines the events that predispose a vein to the development of thrombophlebitis. Trauma to the endothelium of the vein wall results in exposure of subendothelial tissues to platelets. With venous stasis, platelet aggregates form on the vein wall and deposition of fibrin, leukocytes, and erythrocytes results in a free-floating thrombus. Within 7–10 days, this thrombus becomes adherent to the vein wall and secondary inflammatory changes develop, though a free-floating tail may persist. The thrombus is ultimately invaded by fibroblasts, resulting in neovascularization and scarring of the vein wall and destruction of the valves. Central recanalization usually follows, with restoration of flow through the vein; however, because the valves are damaged irreparably, chronic venous insufficiency with postphlebitis syndrome occurs in approximately 35% of patients. In 80% of cases, the thrombosis begins in the deep veins of the calf. Propagation into the popliteal and femoral veins takes place in approximately 25% of these cases.

Clinical manifestations of thrombophlebitis develop in about 3% of patients undergoing major general surgical procedures, and asymptomatic DVT develops in up to 30%. Certain operations, such as total hip replacement, are associated with appreciably higher incidences of thromboembolic complications. Prolonged bed rest or immobility caused by cardiac failure, stroke, ventilatory support, pelvic bone or limb fracture, paralysis, extended air travel, or a lengthy operative procedure is one contributing factor. A hypercoagulable state resulting from malignancy, nephrotic syndrome, inherited deficiency in protein C or S or antithrombin III, homocystinuria, factor V Leiden mutation, or paroxysmal nocturnal hemoglobinuria may also play a role. Other risk factors for DVT include advanced age, type A blood group, obesity, previous thrombosis, multiparity, use of oral contraceptives, inflammatory bowel disease, and lupus erythematosus. Oral contraceptives should be avoided in women who smoke or who have a history of phlebitis because of the high associated risk of thrombotic disease.

Clinical Findings

A. Symptoms and Signs

Fifty percent of patients with thrombophlebitis and 60–70% with acute pulmonary embolism have no symptoms or signs in the involved extremity. Symptomatic

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patients with DVT may complain of a dull ache, tightness, or pain in the calf or leg, especially when walking. Physical examination may disclose slight edema of the involved calf, a palpable cord, distention of the superficial venous collaterals, or low-grade fever and tachycardia. Homans' sign (pain on passive dorsiflexion of the ankle) is positive in only 50% of cases. Iliofemoral venous thrombosis can result in cyanosis of the skin (phlegmasia cerulea dolens) or a pale, cool extremity if reflex arterial spasm is superimposed (phlegmasia alba dolens).

B. Diagnostic Techniques

Because of the difficulty in making a precise diagnosis by history and physical examination and because of the morbidity associated with treatment, diagnostic studies should be used liberally.

1. Duplex ultrasonography

Duplex ultrasonography, because of its high sensitivity, specificity, and reproducibility, has supplanted venography as the most widely used diagnostic test in the initial evaluation of patients in whom this disorder is suspected. The examination includes both a B mode image and Doppler flow analysis. Each venous segment is assessed for the presence of thrombosis, indicated by venous dilation and incompressibility during light probe pressure. Doppler findings suggestive of acute thrombosis are absence of spontaneous flow, loss of flow variation with respiration, and failure to increase flow velocity with distal augmentation. The criteria for the presence of chronic venous thrombosis are less well established. The chronically occluded vein is often narrowed, and there are prominent nearby collaterals. Chronic thrombi are highly echogenic, whereas acute thrombi are anechoic (and therefore not visible) on the B mode image.

2. Ascending contrast venography

This study is used rarely because it is invasive and exposes the patient to ionizing radiation and the risks of contrast allergy, contrast-induced nephropathy, and phlebitis. Patients in whom DVT is strongly suspected but ultrasound is equivocal are now being referred for gadolinium-enhanced magnetic resonance venography. In experienced hands, this examination has a sensitivity of 100% and a specificity of 96% and may provide some information about the age of the thrombus.

3. D-dimer test

Recent evidence suggests that a negative D-dimer test in a patient in whom DVT is suspected is sufficient to omit ultrasound testing.

Differential Diagnosis

Localized muscle strain or contusion or Achilles tendon rupture can often mimic thrombophlebitis. Cellulitis can have a similar clinical presentation: edema, localized pain, and erythema. Other causes of unilateral leg edema (lymphedema, rupture of a Baker cyst, obstruction of the popliteal vein by a Baker cyst, obstruction of the iliac vein by tumor or fibrosis, or external compression of the left iliac vein by the right common iliac artery, known as May-Thurner syndrome) and bilateral leg edema (heart, liver, or kidney failure, or vena caval obstruction by tumor, retroperitoneal fibrosis, or pregnancy) must be excluded.

Complications

Complications of DVT include pulmonary embolism (see Chapter 9), varicose veins, and chronic venous insufficiency.

Prevention

Prophylactic measures may diminish the incidence of venous thrombosis in hospitalized patients. Choice of therapy is dependent on stratification of individual patient risk factors.

A. Nonpharmacologic Measures

Venous stasis can be minimized by several simple maneuvers. Elevation of the foot of the bed 15–20 degrees encourages venous outflow. Slight flexion of the knees is desirable. A footboard enables the patient to perform leg exercises (ankle flexion and extension) while in bed. Sitting in a chair for long periods in the early postoperative period should be avoided. Early ambulation is ideal. Graduated compression stockings and sequential compression devices have proven efficacy in reducing risk of calf vein thrombosis and are particularly useful in moderate-risk and high-risk patients in whom anticoagulation is contraindicated. They function by increasing venous flow, decreasing venous stasis, and increasing the release of endothelial fibrinolytic factors and are safe for use on almost all patients. They have not been shown to decrease the incidence of pulmonary emboli.

B. Anticoagulation

Low-dose unfractionated heparin, 5000 units subcutaneously twice daily, and low-molecular-weight heparin (LMWH), eg, with enoxaparin, 30 mg subcutaneously twice daily, have both been shown to reduce significantly the incidence of postoperative DVT and pulmonary embolism. LMWH appears to be more effective in the orthopedic surgery patient and is associated also with a lower risk of bleeding complications (1–5% with enoxaparin versus 2–12% with unfractionated heparin). Use of heparin products is contraindicated in patients with recent craniotomy, intracranial bleeding, or severe gastrointestinal bleeding. Either medication must be withheld 12 hours prior to placement or removal of an epidural catheter to avoid epidural hematoma. Coagulation studies are unaffected with prophylactic dosing, but the platelet count must be monitored for early detection of heparin-induced thrombocytopenia, which occurs with peak incidence at 5–10 days of treatment. Warfarin is seldom used for perioperative DVT prophylaxis except for orthopedic surgery, but may be indicated for long-term management of minimally ambulatory patients. Lifetime anticoagulation

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with low-dose warfarin or prophylactic vena caval filter placement is considered in patients with hypercoagulable state or paralysis.

Treatment

The standard treatment of DVT is systemic anticoagulation with heparin (initial bolus 100 units/kg followed by 10 units/kg/h, dosed to a goal partial thromboplastin time of 1.5–2 times normal). This reduces the risk of pulmonary embolism and decreases the rate of thrombophlebitis recurrence by 80%. Systemic anticoagulation does not directly lyse thrombi but stops propagation and allows natural fibrinolysis to occur.

Warfarin is started after therapeutic heparinization. The two therapies should overlap to diminish the possibility of a hypercoagulable state, which can occur during the first few days of warfarin administration because warfarin also inhibits synthesis of the natural anticoagulant proteins C and S. The recommended treatment for the first episode of uncomplicated DVT is 3–6 months of warfarin to maintain a goal INR of 2.0–3.0. After a second episode, warfarin is continued indefinitely. The risk for recurrent venous thrombosis is increased markedly in the presence of factor V Leiden mutations, homozygous activated protein C resistance, antiphospholipid antibody, and deficiencies of antithrombin III and of protein C or protein S, so lifelong anticoagulation is also recommended for these conditions.

Recently, enoxaparin at therapeutic dosing (1 mg/kg subcutaneously twice daily) has been shown to be equally safe and effective for treatment of DVT. Enoxaparin does not require monitoring of its anticoagulant effect because of its predictable dose-response relationship, so it has been promoted for use in outpatient treatment. Unfractionated heparin inhibits thrombin by complexing thrombin and antithrombin III. The enoxaparin molecule is too small to inhibit thrombin in this manner; its main therapeutic effect comes from inhibition of factor Xa activity, which accounts for its lower risk of bleeding complications and thrombocytopenia. It has also demonstrated less protein C and S inhibition, less complement activation, and a lower risk of osteoporosis.

Current research efforts are directed toward creation of an oral thrombin inhibitor. This is expected to have a more favorable dose-response curve and side effect profile than warfarin.

Many studies have evaluated the efficacy of fibrinolytic agents in the treatment of acute DVT. Although faster clot lysis and increased venous patency are observed with alteplase versus heparin, this has not translated to a decreased incidence of postphlebitis syndrome. Risk of bleeding complications is higher with alteplase and does not appear to be reduced by selective catheterization for local administration. To be effective, it is felt that alteplase should be instituted within 1 week after clot formation, before extensive fibrin cross-linking can occur. One indication for alteplase is acute iliofemoral venous thrombosis complicated by massive extremity edema and cyanosis. In this setting, iliofemoral thrombectomy is unsuccessful in as many as 50% of patients, often because of an inability to effectively treat distal thrombosis.

Treatment of isolated calf vein thrombosis is controversial, as it is associated with a low risk of pulmonary emboli. However, if untreated, 25% progress to the proximal deep veins, where the incidence of chronic venous insufficiency is 25% and that of fatal pulmonary embolism is 10%. Patients with symptomatic calf vein thrombosis should be anticoagulated; asymptomatic patients may be monitored expectantly with serial ultrasound examination.

Prognosis

With early and effective treatment, prognosis in most cases is good. Mortality is related to pulmonary embolism, which occurs in 60% of patients with inadequately treated proximal lower extremity thrombosis.

Goodacre S et al: Meta-analysis: The value of clinical assessment in the diagnosis of deep venous thrombosis. Ann Intern Med 2005;143:129.

Merli G: Anticoagulants in the treatment of deep vein thrombosis. Am J Med 2005;118(Suppl 8A):13S.

Wells PS et al: Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med 2003;349:1203.

Winter M et al; Haemostoasis and Thrombosis Task Force of the British Committee for Standards in Haematology: Procedures for the outpatient management of patients with deep venous thrombosis. Clin Lab Haematol 2005;27:61.

Thrombophlebitis of the Superficial Veins

Essentials of Diagnosis

  • Induration, redness, and tenderness along a superficial vein.

  • Often a history of recent intravenous line or trauma. No significant swelling of the extremity.

General Considerations

Superficial thrombophlebitis may occur spontaneously in patients with varicose veins, in pregnant or postpartum women, or in patients with thromboangiitis obliterans or Behçet's disease. It can also occur after trauma, such as a blow to the leg, or after intravenous infusion. A migratory thrombophlebitis may be a manifestation of abdominal cancer such as carcinoma of the pancreas (Trousseau's syndrome). The long saphenous vein and its tributaries are most often involved. Superficial thrombophlebitis is associated with occult DVT in

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about 20% of cases. Pulmonary emboli are rare unless extension into the deep venous system occurs.

Clinical Findings

The patient usually experiences a dull pain in the region of the involved vein. Induration, redness, and tenderness correspond to dilated, thrombosed superficial veins. Edema of the extremity and deep calf tenderness are absent unless the deep veins are involved. Chills and high fever suggest septic or suppurative phlebitis, which is most often encountered as a complication of an indwelling intravenous catheter. Plastic intravenous catheters should be observed daily for signs of local inflammation and removed if a local reaction develops to avoid serious thrombotic or septic complications.

Differential Diagnosis

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

Treatment

The primary treatment of superficial venous thrombophlebitis is the administration of nonsteroidal anti-inflammatory drugs, local heat, and elevation. Ambulation is encouraged. In the majority of circumstances, symptoms will resolve within 7–10 days. Excision of the involved vein is recommended for symptoms that persist over 2 weeks on treatment, or for recurrent phlebitis in the same vein segment. If there is progressive proximal extension to the saphenofemoral junction or cephalic-subclavian junction, ligation and resection of the vein at the junction should be performed. Anticoagulation is reserved for rapidly progressing disease or extension into the deep vein system.

Septic thrombophlebitis requires treatment with intravenous antibiotics. As the causative organism is often Staphylococcus or a gram-negative rod, broad-spectrum antibiotic coverage should be instituted until blood culture results become available. If rapid resolution of the phlebitis occurs, no treatment beyond a 7- to 10-day course of antibiotics is required. However, if the patient becomes septic, immediate excision of the infected vein is required.

Prognosis

The course is generally benign and brief, and the prognosis depends on the underlying pathologic process. Phlebitis of a saphenous vein occasionally extends to the deep veins, in which case pulmonary emboli may occur.

Leon L et al: Clinical significance of superficial vein thrombosis. Eur J Vasc Endovasc Surg 2005;29:10.

Chronic Venous Insufficiency

Essentials of Diagnosis

  • History of phlebitis or leg injury.

  • Ankle edema is the earliest sign.

  • Late signs are stasis pigmentation, dermatitis, subcutaneous induration, varicosities, and ulceration.

General Considerations

Chronic venous insufficiency is most often secondary to DVT, although a history of phlebitis is not obtainable in about 25% of patients. Other possible causes are leg trauma, varicose veins, neoplastic obstruction of the pelvic veins, or congenital or acquired arteriovenous fistula.

The basic physiologic abnormality in patients with chronic venous insufficiency is chronic elevation in venous pressure. The normal venous capacitance can accommodate large-volume changes that occur during exercise with only minimal changes in venous pressure. However, when valves in the deep or perforating veins are destroyed by thrombophlebitis, valvular reflux and bidirectional blood flow result in abnormally high ambulatory venous pressures. Proximal venous obstruction also results in venous hypertension. High ambulatory venous pressure transmitted through perforating veins of the calf and ankle results in superficial varicosities, edema and fibrosis of the subcutaneous tissue and skin, hyperpigmentation and, later, dermatitis and ulceration.

Clinical Findings

Chronic venous insufficiency is characterized by progressive edema of the leg that begins at the ankle and calf and is accompanied by a dull aching discomfort. Typically, the edema is worst at the end of the day and improves with leg elevation. Varicosities are often present. Stasis dermatitis, brownish pigmentation, brawny induration, and ulceration develop with long-standing disease. The skin is usually thin, shiny, atrophic, and cyanotic. Cellulitis may appear in scaly, dry, itchy regions with skin breakdown; in other areas, a weeping dermatitis may develop. Venous stasis ulcers are large, painless, and irregular in outline. They have a shallow, moist granulation bed and occur in the gaiter area on the medial or lateral aspects of the ankle. Healing of these ulcers results in a thin scar on a fibrotic base that often breaks down with minor trauma.

Differential Diagnosis

Congestive heart failure and chronic renal disease may result in bilateral edema of the lower extremities. Lymphedema is associated with a brawny thickening in the subcutaneous tissue that does not respond readily to elevation; edema is particularly prominent on the dorsum of the feet and in the toes; varicosities are absent, and there is often a history of recurrent cellulitis.

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Primary varicose veins or acute DVT may be difficult to differentiate from chronic venous insufficiency without diagnostic tests.

Other conditions associated with chronic ulcers of the leg include autoimmune diseases (eg, Felty's syndrome), arterial insufficiency (often painful, well circumscribed, and located over pressure points), sickle cell anemia, erythema induratum (bilateral and usually on the posterior aspect of the lower part of the leg), and fungal infections (cultures specific; no chronic swelling or varicosities).

Prevention

The irreversible tissue changes that accompany chronic venous stasis disease can be minimized by early and aggressive management of conditions associated with deep venous reflux such as acute DVT and varicose veins.

Treatment

A. General Measures

The key to successful management of chronic venous stasis disease is the realization that it is an incurable but manageable problem. Most patients respond to a conservative treatment program. The causes of complications of chronic venous insufficiency are largely mechanical, and so the solutions are mechanical. Bed rest with leg elevation is fundamental in the treatment of the acute complications. Similarly, long-term care of the leg includes (1) intermittent elevation of the legs during the day and elevation of the legs at night (kept above the level of the heart with pillows under the mattress), (2) avoidance of long periods of sitting or standing, (3) the daily use of fitted knee-high or thigh-high graduated compression stockings (20–30 mm Hg), and (4) regular exercise.

B. Management of Stasis Dermatitis

Eczematous eruption may be acute or chronic; treatment varies accordingly. The simplest treatment for acute weeping dermatitis is strict bed rest, leg elevation, and wet saline compresses. Antiseptic solutions containing peroxide, boric acid, or buffered aluminum acetate (Burow's solution) are not recommended because they impede wound healing. Cadexomer iodine is an iodine-containing starch powder dressing that has been shown to speed healing of weepy ulcers. Alginate dressings are also effective in this setting. In general, however, no definitive advantage has emerged of occlusive over semiocclusive dressings or of topical antibiotics, growth factors, or free radical scavengers over simple inert dressings.

Systemic antibiotics and topical antifungal agents (1% clotrimazole or 2% miconazole cream) are indicated only if active infection is suspected. With reduction of the acute edema, 0.5% hydrocortisone cream is applied to the area for 1–2 weeks or until no further improvement is noted. Cordran tape, a plastic tape impregnated with flurandrenolide, is a convenient way to apply both medication and dressing. Zinc oxide ointment with ichthammol, 3%, applied once or twice daily, is an alternative treatment for chronic dermatitis.

C. Ulceration

Venous ulcerations can be treated by wet-to-dry normal saline dressings and Ace wrap compression, or with an Unna boot. The Unna boot is a layered dressing composed of a medicated bandage (such as the original Dome paste composed of calamine, zinc oxide, glycerin, sorbitol, gelatin, and magnesium aluminum silicate), followed by a gauze dressing, followed by an elastic wrap. It must be kept dry and is usually changed weekly. Occasionally, the ulcer is so large and chronic that wide debridement and skin grafting are the best approach. This can be combined with open or endoscopic ligation of incompetent perforating veins contributing to elevated venous pressure in the ulcer bed. Venous reconstructive surgery is performed in some centers for intractable chronic venous stasis disease. The goal of the surgery is to increase venous outflow and decrease venous hypertension in the limb by repairing or replacing incompetent valves in the deep system. Valvuloplasty, venous segment transposition, and valvular transplantation have been performed with variable reported success rates.

Prognosis

Recurrent venous stasis ulcers and progressive venous stasis changes of the skin are not uncommon, particularly if patients do not adhere to a lifelong routine of intermittent leg elevation, regular exercise, and use of graduated compression stockings.

Barwell JR et al: Comparison of surgery and compression with compression alone in chronic venous ulceration (ESCHAR study): randomised controlled trial. Lancet 2004;363: 1854.

Beebe-Dimmer JL et al: The epidemiology of chronic venous insufficiency and varicose veins. Ann Epidemiol 2005;15:175.

Kahn SR et al: Relationship between deep venous thrombosis and the postthrombotic syndrome. Arch Intern Med 2004; 164:17.

Superior Vena Cava Obstruction

Superior vena cava syndrome is a rare disorder caused by partial or complete obstruction of the superior vena cava. The most frequent causes are (1) superior mediastinal tumors (responsible for over 80% of cases), such as adenocarcinoma of the lung, lymphoma, thyroid carcinoma, thymoma, teratoma, synovial cell carcinoma, or angiosarcoma; (2) chronic fibrotic mediastinitis, either idiopathic or secondary to tuberculosis, histoplasmosis, pyogenic infections, or drugs (such as methysergide); (3) thrombophlebitis secondary to indwelling central venous catheters or pacemaker wires; (4) aneurysm of the aortic arch; and (5) constrictive pericarditis.

Clinical Findings

A. Symptoms and Signs

Symptoms include swelling of the neck and face, headache, dizziness, visual disturbances, stupor, and syncope

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related to progressive obstruction of the venous drainage of the head, neck, and upper extremities. Bending over or lying down accentuates the symptoms; sitting quietly is generally preferred. The severity of symptoms is dependent on the degree and duration of stenosis and the development of venous collateral circulation. Dilated anterior chest wall veins and facial flushing ultimately can progress to brawny edema and cyanosis of the face and arms. Cerebral and laryngeal edema result in impaired mental status and respiratory insufficiency.

B. Diagnosis

Diagnosis is usually suggested by the history and physical examination. Duplex ultrasound can be suggestive, but more specific anatomic information is obtained with CT scan or MRA, which can also disclose etiologic causes. Contrast venography is reserved for cases in which surgical or endoscopic treatment is anticipated.

Treatment

Therapy is dictated by the cause of the disease and the severity of symptoms. Benign thrombosis is treated with central venous catheter removal, head elevation, and short-course warfarin anticoagulation or thrombolysis and venous angioplasty. Venous bypass (left atrial appendage to internal jugular or innominate vein) has good patency rates in selected patients refractory to more conservative measures. Surgical excision of the fibrous tissue encasing the great vessels may reestablish flow in patients with mediastinal fibrosis or pericardial constriction. Unless concomitant tumor resection is planned, superior vena cava syndrome secondary to malignant disease is preferentially treated by endovascular stenting. Chemotherapy or external beam radiation may also achieve symptomatic improvement in patients with malignancy.

Bays S et al: Fibrosing mediastinitis as a cause of superior vena cava syndrome. Eur J Cardiothorac Surg 2004;26:453.

Urruticoechea A et al: Treatment of malignant superior vena cava syndrome by endovascular stent insertion. Experience on 52 patients with lung cancer. Lung Cancer 2004;43:209.

Diseases of the Lymphatic Channels

Lymphangitis & Lymphadenitis

Essentials of Diagnosis

  • Red streak extending from an infected area toward enlarged, tender regional lymph nodes.

  • Chills, fever, and malaise may be present.

General Considerations

Lymphangitis and lymphadenitis frequently accompany a streptococcal or staphylococcal infection in the distal arm or leg. The inciting wound may be a superficial scratch with cellulitis, an insect bite, or an established abscess. A prominent red streak extending toward tender, enlarged regional lymph nodes is diagnostic. Systemic manifestations include fever, chills, tachycardia, and malaise. If untreated, the infection can progress rapidly, often in a matter of hours.

Clinical Findings

A. Symptoms and Signs

Throbbing pain at the site of the inciting wound is usually present. Malaise, anorexia, sweating, chills, and fever of 37.8–40°C develop rapidly. The red streak may be faint initially and easily missed, especially in dark-skinned patients. The involved regional lymph nodes may be significantly enlarged and tender.

B. Laboratory Findings

Leukocytosis with a left shift is usually present. Blood cultures are often positive for staphylococcal or streptococcal species. Wound cultures may be helpful in the treatment of more severe or refractory infections but are often difficult to interpret because of skin contaminants.

Differential Diagnosis

Superficial thrombophlebitis is distinguished from lymphangitis by the pattern of erythema (localized to an indurated thrombosed vein) and the lack of lymphadenitis. Cat-scratch disease caused by Bartonella henselae typically presents with enlarged but nontender lymph nodes. Lymphangitis must also be differentiated from cellulitis and from severe soft tissue infections such as acute streptococcal hemolytic gangrene and necrotizing fasciitis requiring emergent debridement. These infections are nonlinear and are characterized by induration and subcutaneous crepitus.

Treatment

The extremity is elevated, and warm compresses are applied to the involved area. Analgesics and intravenous antibiotics (penicillin G, 4 million units every 6 hours, or cefazolin, 1 g every 8 hours) should be instituted immediately. Examination of the wound will determine the need for debridement or incision and drainage of an abscess.

Prognosis

Early institution of appropriate antibiotic therapy and wound care will usually control the infection in 48–72 hours. Delayed or inadequate therapy can

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result in rapidly progressive infection, septicemia, and death.

Badger C et al: Antibiotics/anti-inflammatories for reducing acute inflammatory episodes in lymphoedema of the limbs. Cochrane Database Syst Rev 2004;(2):CD003143.

Lymphedema

Essentials of Diagnosis

  • Painless edema of upper or lower extremities.

  • Involves the dorsal surfaces of the hands and fingers or the feet and toes.

  • Developmental or acquired, unilateral or bilateral.

  • Edema is pitting initially and becomes brawny and nonpitting with time.

  • Ulceration, varicosities, and stasis pigmentation do not occur. There may be episodes of lymphangitis and cellulitis.

General Considerations

The underlying mechanism in lymphedema is impairment of the flow of lymph from an extremity. When due to congenital developmental abnormalities consisting of hypoplastic or hyperplastic changes of the proximal or distal lymphatics, it is referred to as primary lymphedema. Familial lymphedema developing before 1 year of age is called Milroy's disease; it is usually bilateral and affects boys more often than girls. More commonly, lymphedema develops during adolescence (lymphedema praecox) and is unilateral; there is a 3.5:1 female predominance. Lymphedema occurring after age 35 years is referred to as lymphedema tarda. The secondary form of lymphedema results from an inflammatory or mechanical obstruction of the lymphatics following trauma, regional lymph node resection, irradiation, bacterial or fungal infections, lymphoproliferative diseases, or filariasis.

Lymphatic obstruction results in stasis of a protein-rich fluid, with slowly progressive, painless edema and secondary fibrosis that may be exacerbated by superimposed episodes of acute infection. The edema is usually centered around the ankle and involves the toes and the dorsum of the foot. Hypertrophy of the limb results, with markedly thickened skin and subcutaneous tissue. Rarely, lymphangiosarcoma or angiosarcoma may develop as a complication of chronic lymphedema. This neoplastic transformation of blood vessels and lymphatics is called the Stewart-Treves syndrome.

Diagnosis is usually made on the basis of clinical findings. Venous duplex ultrasonography is performed to exclude venous insufficiency or vascular malformations. Lymphangiography and radioactive isotope studies are indicated only if surgical reconstruction is anticipated.

Treatment

Lymphedema is a chronic disease for which there is no complete cure. However, a variety of conservative measures can substantially reduce the risk of further complications and disability. No drug therapy is effective. Use of benzopyrones (eg, dicumarol) and corticosteroid injections to increase lymphatic transport has not shown consistent benefit. Diuretics can be useful for acute exacerbation of edema secondary to infection or for coexisting venous stasis disease but are not recommended for long-term use.

The mainstay of treatment is external compression and meticulous skin care. Mechanical reduction of lymphedema can best be achieved with a program of frequent leg elevation, manual lymphatic drainage massage, and external compression. Sequential pneumatic compression devices are traditionally the first line of treatment for limb reduction. Many different devices are available for use on the leg, and Reid sleeves can be custom fit for patients with postmastectomy arm lymphedema. Graduated compression stockings (20–30 mm Hg) maintain the limb after reduction by pneumatic compression.

Good skin care is imperative to prevent infection. Moisturizing lotions should be applied regularly, especially after showering or bathing. Drying and cracking of the skin can create portals of entry for bacteria. Infection is difficult to eradicate because of disordered lymphatic drainage and can be a threat to limb survival.

In carefully selected cases, surgery may improve limb function. The goal is to reduce limb bulk, either by ablative techniques (excision of excess tissue) or by physiologic techniques (lymphatic reconstruction). Microsurgical lymphaticovenous anastomosis has yielded some satisfactory cosmetic and functional results, though long-term efficacy is as yet unknown.

Hinrichs CS et al: Lymphedema secondary to postmastectomy radiation: incidence and risk factors. Ann Surg Oncol 2004; 11:573.

Kligman L et al: The treatment of lymphedema related to breast cancer: a systematic review and evidence summary. Support Care Cancer 2004;12:421.

Northup KA et al: Syndromic classification of hereditary lymphedema. Lymphology 2003;36:162.

Ozaslan C et al: Lymphedema after treatment of breast cancer. Am J Surg 2004;187:69.

Sieggreen MY et al: Current concepts in lymphedema management. Adv Skin Wound Care 2004;17(4 Pt 1):174.

Taylor MJ et al: Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial. Lancet. 2005;365:2116.

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Hypotension & Shock

Essentials of Diagnosis

  • Hypotension, tachycardia, oliguria, altered mental status.

  • Peripheral hypoperfusion and hypoxia.

General Considerations

Shock occurs when the rate of arterial blood flow is inadequate to meet tissue metabolic needs. Tissue oxygen delivery is dependent on cardiac output, hemoglobin saturation, and peripheral microcirculation—some or all of these factors are altered in the shock state. The physiologic response to shock is mediated by the neuroendocrine system through release of catecholamines, renin, antidiuretic hormone, glucagon, cortisol, and growth hormone. These hormones are responsible for many of the clinical manifestations of shock: tachycardia, oliguria, delayed capillary refill, increasing agitation, and insulin resistance. Treatment must be directed both at the manifestations of shock and at its cause.

Classification

A. Hypovolemic Shock

Decreased intravascular volume resulting from loss of blood, plasma, or fluids and electrolytes may be obvious (eg, external hemorrhage) or subtle (eg, sequestration in a “third space”) (Table 12-1). Compensatory vasoconstriction temporarily reduces the size of the vascular bed and may transiently maintain the blood pressure, but unreplaced ongoing losses of over 15% of the blood volume result in hypotension, increased peripheral resistance, collapse of capillary and venous beds, and progressive tissue hypoxia. Even a moderate sudden loss of circulating fluids can result in severe damage to vital organs.

B. Cardiogenic Shock

Pump failure can be related to myocardial infarction, cardiomyopathy, myocardial contusion, valvular incompetence or stenosis, or arrhythmias (Table 12-1). See discussion in Chapter 10.

C. Obstructive Shock

Cardiac tamponade, tension pneumothorax, and massive pulmonary embolism can cause an acute decrease in cardiac output resulting in shock (Table 12-1). These are medical emergencies requiring prompt diagnosis and treatment. Pericardiocentesis or pericardial window, chest tube placement, or catheter-directed thrombolytic therapy can be lifesaving.

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

Hypovolemic shock
   Loss of blood (hemorrhagic shock)
      External hemorrhage
         Trauma
         Gastrointestinal tract bleeding
      Internal hemorrhage
         Hematoma
         Hemothorax or hemoperitoneum
   Loss of plasma
      Burns
      Exfoliative dermatitis
   Loss of fluid and electrolytes
      External
         Vomiting
         Diarrhea
         Excessive sweating
         Hyperosmolar states (diabetic ketoacidosis, hyperosmolar nonketotic coma)
   Internal (“third spacing”)
         Pancreatitis
         Ascites
         Bowel obstruction
Cardiogenic shock
   Dysrhythmia
      Tachyarrhythmia
      Bradyarrhythmia
   “Pump failure” (secondary to myocardial infarction or other cardiomyopathy)
   Acute valvular dysfunction (especially regurgitant lesions)
   Rupture of ventricular septum or free ventricular wall
Obstructive shock
   Tension pneumothorax
   Pericardial disease (tamponade, constriction)
   Disease of pulmonary vasculature (massive pulmonary emboli, pulmonary hypertension)
   Cardiac tumor (atrial myxoma)
   Left atrial mural thrombus
   Obstructive valvular disease (aortic or mitral stenosis)
Distributive shock
   Septic shock
   Anaphylactic shock
   Neurogenic shock
   Vasodilator drugs
   Acute adrenal insufficiency
Reproduced, with permission, from Saunders CE, Ho MT (editors): Current Emergency Diagnosis & Treatment, 4th ed. McGraw-Hill, 1992.

D. Distributive Shock

Reduction in systemic vascular resistance from sepsis, anaphylaxis, systemic inflammatory response syndrome (SIRS) produced by severe pancreatitis or burns, or acute adrenal insufficiency may result in inadequate cardiac output despite normal circulatory volume (Table 12-1). Elevated nitric oxide levels may explain many of the physiologic aspects of the disease.

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1. Septic shock

Sepsis is the most common cause of distributive shock and carries a mortality of 40–80%. Typically, patients present with fever, chills, hypotension, hyperglycemia, and altered mental status due to gram-negative bacteremia (E coli, Klebsiella, Proteus, and Pseudomonas). Gram-positive cocci and gram-negative anaerobes (Bacteroides) are less often implicated. Risk factors include extremes of age, diabetes, immunosuppression, and recent urinary, biliary, or gynecologic manipulation, such as placement of a percutaneous nephrostomy or biliary drain in an obstructed system.

2. Neurogenic shock

Neurogenic shock is caused by traumatic spinal cord injury or effects of an epidural or spinal anesthetic. Reflex vagal parasympathetic stimulation evoked by pain, gastric dilation, or fright may simulate neurogenic shock, producing hypotension, bradycardia, and syncope.

Diagnosis of Shock & Impending Shock

The different types of shock are characterized by the same clinical signs.

A. Hypotension

Hypotension in adults is traditionally defined as a systolic blood pressure of 90 mm Hg or less but must be evaluated relative to the patient's normal blood pressure. Whereas a systolic blood pressure of 90 mm Hg may be normal in a healthy, athletic adult, a pressure of 100 mm Hg may indicate shock in a patient who is normally hypertensive. A drop in systolic pressure of more than 10–20 mm Hg and an increase in pulse of more than 15 with positional change suggest depleted intravascular volume. Orthostatic hypotension resulting from peripheral neuropathy or use of β-blockers is usually not associated with an increase in pulse rate.

B. End-Organ Hypoperfusion

Patients in shock often have cool or mottled extremities and weak or absent peripheral pulses. Splanchnic vasoconstriction leads to oliguria, bowel ischemia, and hepatic dysfunction, which can ultimately result in multiorgan failure.

C. Altered Mental Status

Patients may demonstrate normal mental status or may be restless, agitated, confused, lethargic, or comatose as a result of inadequate perfusion of the brain.

Treatment

A. General Measures

Treatment depends on prompt diagnosis and an accurate appraisal of inciting conditions. Initial therapy consists of basic life support: airway maintenance, oxygen, cardiopulmonary resuscitation, intravenous access, and fluid resuscitation. Cardiac monitoring can detect myocardial ischemia requiring cardiac catheterization and thrombolytic therapy or malignant arrhythmias treated by standard advanced cardiac life support (ACLS) protocols. A thorough history and physical examination, including stool guaiac testing, is helpful in locating potential sources of sepsis or hemorrhage and excluding immediately reversible causes such as tamponade or tension pneumothorax. Unresponsive or minimally responsive patients are immediately given 50% dextrose (one ampule intravenously) and naloxone (2 mg intravenously or intramuscularly) followed by neurologic assessment (Glasgow Coma Scale) and are then intubated for airway protection. Specimens should be sent for complete blood count, electrolytes, glucose, arterial blood gas determinations, coagulation parameters, and typing and cross-matching. An arterial line is placed for continuous blood pressure measurement and a Foley catheter for assessment of urine volume. Urinary output should be maintained at > 0.5 mL/kg/h.

Early consideration is given to placement of a pulmonary artery catheter for hemodynamic pressure measurements or transthoracic echocardiography. This is helpful in distinguishing cardiogenic and septic shock and in monitoring the effects of volume resuscitation or pressor medications. Because of the attendant risks associated with pulmonary artery catheters (infection, arrhythmias, vein thrombosis, pulmonary artery rupture), the value of the information they might provide must be carefully weighed in each patient. They are useful in the management of patients with cardiogenic shock; in other types of shock, a central venous line may be adequate. Central lines may also be useful in the administration of medications and in the measurement of central venous oxygen saturation. In general, a central venous pressure (CVP) or pulmonary capillary wedge pressure (PCWP) under 5 mm Hg suggests hypovolemia and over 18 mm Hg suggests volume overload, cardiac failure, tamponade, or pulmonary hypertension. A cardiac index < 2 L/min/m2 indicates a need for pharmacologic or mechanical pressor support. A high cardiac index (> 4 L/min/m2) in a hypotensive patient is consistent with early septic shock. The systemic vascular resistance (SVR) is a derived value and is low (< 800 dyn · s/cm5) in early sepsis and neurogenic shock and high (> 1500 dyn · s/cm5) 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 central venous oxygen saturation of greater than 70%.

B. Volume Replacement

Hypovolemic shock is treated with fluid resuscitation. Initial response is gauged after bolus administration of 2 L of crystalloid, and additional fluid requirements are then estimated from measurement of ongoing losses, CVP or PCWP, and urinary output.

Selection of the proper fluid for restoration and maintenance of hemodynamic stability is controversial. Blood products are indicated in hemorrhagic shock; type-specific or type O negative packed red blood cells (PRBC) are given to maintain the hematocrit above 30%. Whole blood provides extra volume and clotting factors. Each unit of PRBC or whole blood is expected to raise the hematocrit

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by 3%. With abnormal coagulation studies, platelet count less than 10,000/mcL, or transfusion of over six units of PRBC, fresh frozen plasma and platelets should be administered. When hematocrit is greater than 30% and CVP is less than 8 mm Hg, crystalloid solutions are generally the preferred resuscitation fluid. Isotonic (0.9%) sodium chloride or lactated Ringer's solution (which contains potassium, calcium, and bicarbonate as well as sodium chloride) is given in boluses of 500 mL or 1000 mL. Dextrose-containing solutions are generally not needed initially except in the treatment of hypoglycemic shock. Hypertonic (7.5%) saline is being investigated for use in the prehospital setting and in the hypotensive patient with closed head injury.

Plasma expanders—or colloids such as albumin, dextran, and hetastarch—are high-molecular-weight substances that increase plasma oncotic pressure. Increased capillary permeability in the lung accompanying septic shock or SIRS may result in increased pulmonary edema in patients administered colloids, so use of these agents warrants careful consideration. Side effects include coagulopathy and anaphylaxis. Oxygen-carrying synthetic plasma expanders (“artificial blood”) have been used with success in some trauma centers for treatment of hypovolemic shock.

Large-volume resuscitation with unwarmed fluids produces hypothermia, which must be treated to avoid hypothermia-induced coagulopathy.

C. Medications

Calcium should be administered to maintain an ionized calcium level greater than 1.15 mmol/L. Sodium bicarbonate may be considered in patients with arterial pH less than 7.20.

Pressors are administered only after adequate fluid resuscitation. Dopamine hydrochloride has variable effects according to dosage. At low doses (2–3 mcg/kg/min), stimulation of dopaminergic and β-agonist receptors produces increased glomerular filtration rate, heart rate, and contractility. At higher doses (> 5 mcg/kg/min), α-adrenergic effects predominate, resulting in peripheral vasoconstriction.

Dobutamine (2–20 mcg/kg/min), a synthetic catecholamine with greater inotropic effect and afterload reduction than dopamine, is the first-line drug for cardiogenic shock. Because tachyphylaxis can occur after 48 hours, the phosphodiesterase inhibitor amrinone (5–15 mcg/kg/min) is often substituted. Diuretics, thrombolytics, morphine, nitroglycerin, antiarrhythmics, and antiplatelet agents may be part of a multimodality approach to treatment of cardiogenic shock secondary to acute myocardial infarction.

Distributive shock or neurogenic shock may require peripheral vasoconstrictors such as epinephrine (2–10 mcg/min) or norepinephrine (0.5–30 mcg/min). Phenylephrine is avoided in neurogenic shock because of the potential for reflex bradycardia.

Vasopressin (antidiuretic hormone [ADH]) is gaining widespread acceptance in the treatment of distributive shock and has been added to the ACLS algorithm for ventricular fibrillation cardiac arrest. Shock due to sepsis or SIRS is associated with low levels of endogenous vasopressin; in hemorrhagic shock, vasopressin is initially elevated and then drops to subnormal levels. Vasopressin has multiple therapeutic effects: peripheral vasoconstriction, decreased heart rate, hemostasis, increased serum cortisol, and coronary, cerebral, and pulmonary vasodilation. It has also been shown to potentiate the effects of other peripheral vasoconstrictors. Paradoxically, at low doses (0.01–0.04 units/min), it acts as a diuretic. The dose is regulated to maintain normal physiologic serum levels of 20–30 pg/mL. The effect on mortality rate in septic shock is as yet unknown. Vasopressin-induced vasoconstriction may be mediated by effects on nitric oxide synthesis.

Methylene blue is another inhibitor of the nitric oxide pathway being investigated for use in distributive shock.

Broad-spectrum antibiotics are administered in septic shock until blood cultures and sensitivities become available. Sedation, anxiolytics, and pain medications are tailored for each individual case. Corticosteroids are lifesaving in the treatment of shock associated with acute adrenal insufficiency (see Chapter 26) and decrease inflammation associated with acute spinal shock, but they are of no benefit in other types of shock. Research has focused on regulation of specific inhibitors of the inflammatory response. Protein C levels are diminished in septic shock, and recombinant protein C (drotrecogin alfa) is now in phase 3 trials. It has been shown to significantly decrease 28-day mortality in septic shock when given as a continuous infusion of 24 mcg/kg/h for 96 hours. Its mechanism of action is reduction of systemic inflammation by inhibition of thrombosis. Administration of recombinant protein C has been correlated with lower D-dimer and interleukin-6 levels in this setting.

Other Treatment Modalities

Cardiac failure may require use of transcutaneous or transvenous pacing or placement of an intra-arterial balloon pump. Emergent revascularization by stent angioplasty or coronary artery bypass appears to improve long-term outcome. Urgent hemodialysis or continuous venovenous hemofiltration may be indicated for maintenance of fluid and electrolyte balance during acute renal insufficiency resulting from shock.

Annane D et al: Septic shock. Lancet 2005;365:63.

Duvernoy CS et al: Management of cardiogenic shock attributable to acute myocardial infarction in the reperfusion era. J Intensive Care Med 2005;20:188.

Gluck T et al: Advances in sepsis therapy. Drugs 2004;64:837.

Graham CA et al: Critical care in the emergency department: shock and circulatory support. Emerg Med J 2005;22:17.

Minneci PC et al: Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose. Ann Intern Med 2004;141:47.

Weigand MA et al: The systemic inflammatory response syndrome. Best Pract Res Clin Anaesthesiol 2004;18:455.