Chapter 6. Mesenteric Vascular Disease

Essential Concepts

• Acute mesenteric ischemia (AMI) is a medical and surgical emergency. Delay in diagnosis is associated with high mortality.
• Patients often present with abdominal pain out of proportion to physical examination findings.
• Clinical suspicion of AMI necessitates early radiologic evaluation (computed tomographic [CT] angiography, conventional angiography) or exploratory surgery in patients with peritoneal signs.
• Chronic intestinal ischemia is a clinical diagnosis; patients report classic symptoms (eg, abdominal angina) and have radiographic findings showing severe stenoses or occlusion of two or more mesenteric arteries.
• Colonic ischemia is rarely life threatening and usually resolves with supportive care.

Etiology & Pathogenesis

Intestinal ischemia is caused by a reduction in intestinal blood flow, most commonly as a result of occlusion, vasospasm, or hypoperfusion of the mesenteric circulation. It is categorized as acute or chronic, depending on the rapidity and the extent to which blood flow is compromised and whether it is episodic or constant, as might occur in chronic mesenteric ischemia. Ischemia can involve the small intestine or colon. Acute small intestinal ischemia is a medical and surgical emergency that requires prompt diagnosis and a coordinated, interdisciplinary approach. By contrast, acute colonic ischemia (ie, ischemic colitis) is rarely an emergent condition. Acute intestinal ischemia can be further categorized as arterial versus venous, embolic versus thrombotic, and occlusive versus nonocclusive. Other causes of bowel ischemia include strangulating obstructions (adhesions, hernias, metastatic malignancy, intussusceptions) and vasculitis (systemic lupus erythematosus, polyarteritis nodosa).

Splanchnic Circulation: Anatomy & Physiology

The vascular supply to the intestines includes the celiac artery, the superior mesenteric artery (SMA), and the inferior mesenteric artery (IMA) (Figure 6–1). The celiac axis supplies blood to the stomach and duodenum. The SMA supplies the small bowel from the distal duodenum to the mid-transverse colon. The inferior mesenteric artery supplies the transverse colon to the rectum. Anastomoses exist between branches of the major vessels, and if one artery is occluded, some flow may be maintained via a patent collateral vessel.

When a major vessel is occluded, collateral pathways open immediately in response to a fall in arterial pressure distal to the obstruction. The superior and inferior pancreaticoduodenal vessels are collaterals that connect the celiac axis to the SMA. The phrenic artery connects the aorta to the celiac axis. The marginal artery of Drummond and the arc of Riolan are collaterals that connect the SMA and the IMA. The internal iliac arteries provide collaterals to the rectum. Griffith point in the splenic flexure and Sudeck point in the rectosigmoid area are watershed areas within the colonic blood supply and common locations for ischemia.

The splanchnic circulation receives 25% of the cardiac output under basal conditions and 35% or more postprandially. Approximately 70% of splanchnic inflow goes to the mucosa, which is the most metabolically active area of the gut. The villus tips are the most vulnerable to ischemic injury. Intestinal blood flow is under complex regulation controlled primarily by resistance arterioles and precapillary sphincters. Several vasoactive substances influence intestinal perfusion. Catecholamines, angiotensin II, and vasopressin all can cause vasoconstriction, whereas vasoactive intestinal peptide causes vasodilation. Products of ischemia such as acidosis, hypoxemia, and hyperkalemia have been shown to cause vasodilation. Ischemic damage is caused by both hypoxia and reperfusion injury.

Essentials of Diagnosis

• Maintain a high index of clinical suspicion.
• Consider in patients >50 years who present with sudden onset of severe abdominal pain lasting >2 hours, especially if a history of cardiovascular disease (congestive heart failure, myocardial infarction, arrhythmia) is present.
• Consider in patients with abdominal pain out of proportion to physical findings.
• Angiography is the diagnostic procedure of choice and is potentially therapeutic.

General Considerations

Acute mesenteric ischemia (AMI) remains a challenging diagnosis, with a mortality rate exceeding 50%. The incidence of AMI has increased over the past 20 years due to longer life expectancies, increased awareness of ischemic syndromes, and enhanced diagnostic and therapeutic techniques. The various causes of AMI include SMA embolism (50%), SMA thrombosis (15–20%), nonocclusive mesenteric ischemia (NOMI; 20–25%), and mesenteric venous thrombosis (5–10%).

Mesenteric Artery Embolism & Thrombosis

Embolism to the SMA is most frequently due to a dislodged thrombus originating from the left atrium, left ventricle, or cardiac valves. One third of patients have a history of a prior embolic event, and 20% have synchronous emboli. The onset of symptoms is abrupt and dramatic. SMA thrombosis usually occurs at the origin of the vessel, which is frequently an area of severe atherosclerotic narrowing. Acute thrombosis usually occurs in a patient with underlying chronic intestinal ischemia. This process is analogous to plaque rupture in acute coronary syndromes. Approximately 50% of patients have a history of chronic mesenteric ischemia, and the acute event occurs after closure of a collateral vessel.

Clinical Findings

Symptoms & Signs

Patients with AMI present with severe, acute, unremitting abdominal pain strikingly out of proportion to the initial physical findings. On examination, the abdomen may be soft and either nontender or minimally tender. Distention is often the first sign. Later findings may include signs of peritonitis, especially if infarction or gangrene has occurred. Associated symptoms may include nausea, emesis, and transient diarrhea due to urgent bowel evacuation. Occult blood is found in the stool in 50–75% of cases.

Laboratory Findings

Leukocytosis with a white blood cell count greater than 15,000/μL is found in 75% of patients. However, most patients with early intestinal ischemia do not have abnormal laboratory findings. Lactic acidosis, hemoconcentration, and raised serum aminotransferase levels are usually late findings indicative of intestinal infarction.

Imaging Studies

Historically, standard radiologic imaging has not been useful in diagnosing AMI, because most of the reported "classic" findings (eg, bowel edema, pneumatosis intestinalis, portal venous gas) are not seen until late in the course of the illness. Plain films of the abdomen are usually normal, and the utility of these studies is to exclude other acute abdominal processes such as perforation or obstruction. Mesenteric angiography has been the gold standard for making the diagnosis of AMI; however, recent studies have demonstrated that CT scans may have an overall sensitivity of 80% for AMI, thanks to technical advances, including spiral CT, rapid intravenous bolus injection of contrast, and multidetector-row CT (MDCT) with three-dimensional reconstruction. CT findings may be either more specific or nonspecific. More specific findings include thromboembolism in mesenteric vessels, portal venous gas, bowel wall intramural gas or pneumatosis, lack of bowel wall enhancement, and signs of ischemia in other organs. Less specific signs include diffuse bowel wall thickening, striking vascular engorgement, dilated fluid-filled loops of bowel, and mesenteric edema (Figure 6–2). Magnetic resonance angiography (MRA) can produce similar images; however, image acquisition takes longer than for MDCT, which limits its use in the setting of an acutely ill patient.

Initial evaluation should include radiographic imaging to exclude other causes of acute abdominal pain such as perforation or obstruction. MDCT can provide detailed information about the mesenteric vessels and small bowel and is particularly sensitive in the diagnosis of mesenteric venous thrombosis.

Angiography

Angiography is important in both diagnosis and management of AMI and remains the gold standard for evaluation of patients with suspected AMI and no peritoneal signs. It is the mainstay of diagnosis and treatment for both occlusive mesenteric ischemia and NOMI. It can be both diagnostic and therapeutic. Placement of a catheter into the SMA allows visualization of obstructing lesions and facilitates interventions such as infusion of vasodilators into the SMA, angioplasty, stenting, or infusion of thrombolytics (Figure 6–3).

Treatment

The goal of treatment in AMI is to restore intestinal blood flow as rapidly as possible. However, initial management must include hemodynamic resuscitation and correction of precipitating causes of AMI such as arrhythmias, congestive heart failure, or volume depletion. Patients require aggressive hemodynamic monitoring and support, correction of fluid and electrolyte abnormalities, and treatment with broad-spectrum antibiotics.

Patients with peritoneal signs or clinical suspicion of perforation or gangrene require emergent laparotomy, after hemodynamic stabilization, to immediately restore mesenteric blood flow and resect nonviable bowel. Patients who are hemodynamically stable with no peritoneal signs should undergo angiography to diagnose obstructive lesions and begin treatment with vasodilators, such as papaverine, which when infused directly into mesenteric vessels can help increase blood flow by reversing vasospasm. Once an obstructing lesion is confirmed with angiography, patients can undergo either surgical revascularization (through aortomesenteric bypass grafting, embolectomy, or thromboendarterectomy) or endovascular revascularization (using techniques such as balloon dilation and angioplasty with or without stenting, or catheter-directed thrombolytic therapy, in selected cases). The American Gastroenterological Association algorithm for diagnosis and management of acute intestinal ischemia is presented in Figure 6–4.

Mesenteric Venous Thrombosis

Essentials of Diagnosis

• Acute form—maintain a high index of suspicion in patients with recent onset of acute abdominal pain associated with a predisposing condition (ie, heritable or acquired hypercoagulable states).
• Diagnosed with 90% sensitivity by contrast CT, MDCT, or vascular angiography.

General Considerations

Mesenteric venous thrombosis (MVT) accounts for 5–10% of all cases of AMI. The conditions responsible for the development of MVT can be identified in over 80% of cases, and risk factors are summarized in Table 6–1. The clinical presentation of MVT can be acute, characterized by the sudden onset of symptoms; subacute, in which symptoms occur for days or weeks without bowel infarction; or chronic, involving portal or splenic vein thrombosis and stigmata of portal hypertension with or without variceal bleeding.

Pathogenesis

MVT leads to resistance to mesenteric venous blood flow and intestinal ischemia, with resultant bowel wall edema, fluid efflux into the bowel lumen, and systemic hypotension. As a consequence of venous congestion, arterial inflow is diminished, which can lead to bowel ischemia and, ultimately, infarction. The extent of the venous collateral circulation is a key variable influencing whether submucosal hemorrhage or bowel infarction will develop following MVT.

Clinical Findings

Symptoms and Signs

As noted, the presentation of MVT can be acute, subacute, or chronic. Symptoms of acute MVT usually begin a few days to a few weeks (mean, 7 days) before presentation and, in 25% of patients, have been present for 30 days before admission. Nausea, vomiting, and diarrhea are common, and over 50% of patients have occult blood in the stool. Examination findings include fever (50%), abdominal distention with mild to moderate tenderness and signs of dehydration, and hypotension (25%). Hematochezia, found in 15% of patients, usually signifies severe ischemia or bowel infarction. Fever, guarding, rebound tenderness, lactic acidosis, and increased transaminases are late findings that may be associated with bowel infarction.

In the subacute form of MVT, symptoms such as abdominal pain can be present for several weeks along with an unremarkable physical examination. Patients with chronic MVT may not have experienced abdominal pain and often present with stigmata of portal hypertension, varices (esophageal, gastric, intestinal), and splenomegaly or bleeding from varices. The latter can be manifested by hematemesis or fecal blood loss.

Over 50% of patients with MVT have a personal or family history of deep venous thrombosis or pulmonary embolism. MVT should be suspected in patients with pain out of proportion to physical findings, especially if there is a personal or family history of such coagulation abnormalities.

Imaging Studies

The gold standard for the diagnosis of MVT is CT scan with intravenous contrast. Classical findings with a sensitivity of greater than 90% include a dilated superior mesenteric vein with a clot or filling defect in the lumen (Figure 6–5). It should be noted, however, that CT may be less reliable in early thrombosis if small vessels are involved. Portal venous gas, air in the small bowel, or free intraperitoneal air usually indicates intestinal infarction.

Treatment

The treatment of acute MVT depends on whether intestinal infarction has occurred or is strongly suspected. For example, persistent peritoneal findings such as guarding or rebound tenderness should raise suspicion for gut infarction and warrant laparotomy (see Figure 6–4). By contrast, in patients with clinical and radiologic evidence of MVT, but no infarction, and with good mesenteric blood flow demonstrated by angiography, conservative management can be attempted using anticoagulation therapy (ie, heparin). Anticoagulation is usually continued for 6 months or longer if coagulation abnormalities preceded MVT. Few data are available regarding long-term follow-up or the need for treatment after 6 months. Use of thrombolytics such as streptokinase, urokinase, and tissue plasminogen activator has not been studied in a large group of patients; however, catheter-directed thrombolysis has been performed in some cases.

When there is suspicion of bowel infarction, laparotomy is required to restore mesenteric blood flow and resect gangrenous bowel segment(s). In cases in which there is extensive ischemic damage, massive intestinal resection followed by long-term parenteral nutrition may be required.

Nonocclusive Mesenteric Ischemia

Essentials of Diagnosis

• Accounts for ~20% of cases of AMI and results from intense mesenteric vasoconstriction, leading to splanchnic hypoperfusion.
• Maintain a high index of clinical suspicion.
• Suspect in patients with diffuse atherosclerotic disease under conditions of hemodynamic stress (hypotension), in the setting of vasoconstrictive agents (vasopressin, cocaine), and in patients with vasculitis (eg, systemic lupus erythematosus, polyarteritis nodosa).
• Angiography may be both diagnostic and therapeutic.

Clinical Findings

Signs and symptoms of NOMI may be similar to those of AMI. Patients who develop NOMI are typically elderly with diffuse vascular disease, but NOMI can also be seen in patients with vasculitis or who are on vasoconstricting medications. Predisposing factors include conditions such as myocardial infarction with decreased cardiac output, congestive heart failure, cardiac arrhythmias, sepsis, dehydration, and shock; medications such as diuretics, digoxin, and adrenergic agonists; and therapies such as dialysis. Vasopressin and angiotensin are the most likely mediators of the marked vasoconstriction. NOMI has also been reported after cocaine use.

The mortality rate from NOMI is high for several reasons, including advanced patient age, comorbidities, and difficulty in making the diagnosis and reversing ischemia once it has started. When NOMI is suspected, angiography is the gold standard for diagnosis and management (Figure 6–6).

Treatment

Treatment of NOMI includes hemodynamic resuscitation, antibiotics, and intra-arterial infusion of papaverine, a smooth muscle dilator, which reverses vasoconstriction and restores mesenteric blood flow.

Prognosis in Patients with AMI

Survival of patients with AMI depends on early diagnosis and treatment. Mortality rates from AMI have been reported at 70–90% if diagnosis is delayed and intestinal gangrene develops. However, patients with angiographically proven AMI who do not have peritonitis can have improved survival rates, approaching 90%. Early diagnosis and prompt intervention with angiography, or surgery, or both, are of critical importance for improving outcomes for patients with AMI.

Essentials of Diagnosis

• Postprandial abdominal pain, avoidance of eating (which triggers pain), weight loss, abdominal bruit (50% of patients).
• Angiography shows involvement of at least two of three major splanchnic blood vessels.

General Considerations

Chronic mesenteric ischemia (CMI) is the result of reduced blood flow due to atherosclerotic narrowing of at least two of three major vessels (ie, celiac axis, SMA, or IMA). Usually, an adequate collateral circulation has developed that prevents intestinal infarction. However, acute or chronic mesenteric ischemia and infarction can develop suddenly if thrombosis or embolism occurs in a severely narrowed artery.

Clinical Findings

Symptoms and Signs

The classic diagnostic triad for CMI consists of postprandial abdominal pain, weight loss, and an abdominal bruit. Pain from abdominal angina is typically recurrent, dull, crampy, epigastric, and periumbilical, occurring 10–30 minutes after meals and lasting 1–3 hours. Because eating consistently triggers pain, food fear causes patients to eat progressively less, resulting in weight loss and often cachexia. Most patients have a history of peripheral vascular disease (PVD). It is important to note that some patients with PVD develop abdominal angina after undergoing surgical repair of peripheral vascular lesions because of so-called steal syndrome (ie, increased blood flow to the extremities and away from the mesenteric circulation).

Physical examination of CMI patients usually reveals a soft abdomen without tenderness during episodes of pain, hence the classic description of pain disproportionate to physical findings. As many as 50% of CMI patients have an epigastric bruit, especially postprandially, and nausea, emesis, and early satiety are common associated symptoms. The average duration of symptoms prior to diagnosis is 1 year. Diagnosis is often difficult because of the vague nature of complaints, absence of physical findings, and lack of an accurate noninvasive test.

Imaging Studies

Angiography is the diagnostic test of choice for CMI; however, the diagnosis of CMI remains a clinical rather than an anatomic one. Angiograms in patients with CMI typically demonstrate high-grade stenosis in at least two vessels. CT angiography, magnetic resonance angiography (MRA), and Doppler ultrasound measuring mesenteric blood flow are noninvasive imaging modalities. However, it is important to correlate angiographic findings with symptoms, because some individuals who have complete occlusion of all three major mesenteric arteries may remain asymptomatic because of collateral blood flow. Although there have been preliminary reports of "stress tests" for abdominal angina, at present there is no functional test with high sensitivity or specificity for confirming a clinical diagnosis of CMI.

Treatment

Once the diagnosis of CMI is made based on symptoms and high-grade stenosis or occlusion of two or more mesenteric arteries, the goal is to restore mesenteric arterial flow. Although open surgical revascularization using aortomesenteric grafting is the gold standard, studies suggest that endovascular therapy using percutaneous angioplasty with or without stenting may be effective in treating CMI, albeit with a higher risk of symptom recurrence.

Essentials of Diagnosis

• Typically, sudden onset of left lower quadrant pain followed by hematochezia within 24 hours.
• Diagnosed by colonoscopy or imaging studies (CT, barium enema).
• Bleeding is not massive and transfusion only rarely required.

General Considerations

Colonic ischemia, also referred to as ischemic colitis, is the most frequent form of mesenteric ischemia, accounting for 75% of all intestinal ischemia and affecting primarily the elderly. It is estimated that colonic ischemia may account for as many as 3 per 1000 hospital admissions. Findings of colonic ischemia are seen in 1 of every 100 colonoscopies and may be misdiagnosed as inflammatory bowel disease or infectious colitis (Plate 3). Colonic ischemia has been described in several clinical settings (Table 6–2), although in many instances, no specific cause can be identified. Many cases are initially misdiagnosed as inflammatory bowel disease or infectious colitis, especially in individuals younger than age 50 years. The risk of colonic ischemia appears to be highest for patients who have recently undergone cardiovascular surgery, and these patients may experience more severe episodes.

Pathogenesis

Ischemic injury to the colon usually occurs as a consequence of a sudden and transient reduction in blood flow, resulting in a low-flow state. In the majority of cases, a specific occluding anatomic lesion cannot be identified. Although it may occur anywhere, colonic ischemia most commonly affects the so-called watershed areas with a limited collateral blood supply, such as the splenic flexure and left colon (Figure 6–7). Ischemia is usually mucosal and rarely transmural; consequently, gangrenous colitis and colonic strictures are infrequent. Eighty-five percent of cases of colonic ischemia resolve spontaneously within 2 weeks.

Clinical Findings

Symptoms and Signs

Patients with colonic ischemia usually present with abrupt onset of crampy left lower quadrant abdominal pain, and mild to moderate rectal bleeding or bloody diarrhea within the first 24 hours. Over 90% of patients are older than 60 years. Cardiovascular disease is common, and frequent precipitating factors include hypotension, cardiovascular surgery (coronary artery bypass grafting, aortic aneurism repair), dialysis, and dehydration. Physical examination reveals mild to moderate abdominal tenderness over the affected bowel, most often left-sided.

In contrast to patients with AMI, those with colonic ischemia do not usually appear acutely ill. Bleeding is usually mild, and patients rarely require blood transfusion. Peritoneal signs, if present, would suggest perforation or peritonitis. Ischemic colitis is usually a singular event, and only 5% of patients develop a recurrence.

The diagnosis is usually established on the basis of clinical history, physical examination, and endoscopic or radiologic studies. Although most patients who develop colonic ischemia are elderly, the condition can also occur in younger patients. For patients who are younger than age 50, several precipitants of colonic ischemia should be considered (see Table 6–2). In young women, the triad of smoking, use of oral contraceptives, and carriage of the factor V Leiden mutation may be associated with increased risk of colonic ischemia. Recent reports indicate that giving penicillin derivatives to patients who harbor Klebsiella oxytoca may precipitate hemorrhagic colitis.

Diagnostic Tests

Diagnostic modalities include flexible sigmoidoscopy or colonoscopy, plain films of the abdomen, and CT scan. Colonoscopy with biopsies makes the definitive diagnosis; however, endoscopy should be avoided in patients with significant abdominal pain or distention because air insufflation may precipitate perforation in cases of severe ischemia. Endoscopic findings frequently include petechial bleeding, pale mucosa, and, in more severe cases, hemorrhagic ulceration (see Plate 3), and biopsy specimens show characteristic findings. Plain films of the abdomen are usually nondiagnostic, but thumbprinting representing submucosal hemorrhage and edema may be seen in 20–25% of cases. The use of plain films has been largely superseded by the ready availability and accuracy of CT scans. CT scans can demonstrate wall thickening, mucosal and submucosal hemorrhage, and pericolic fat stranding, and occasionally bowel wall pneumatosis (Figure 6–8).

Angiography is usually not necessary in the evaluation of colonic ischemia; however, it should be considered if the clinical findings raise concern for concomitant small bowel ischemia or infarction.

Stool studies should be performed to exclude infections such as Escherichia coli O157:H7, Campylobacter enteritis, Klebsiella oxytoca, Shigella, or Clostridium difficile, which can be associated with hemorrhagic colitis.

Treatment

Patients with colonic ischemia are usually placed on bowel rest. Patients should be followed with serial abdominal examinations and monitored for bleeding, fever, leukocytosis, and electrolyte abnormalities. Although there are no controlled randomized trials proving the effectiveness of antibiotics in reducing morbidity and mortality, broad-spectrum intravenous antibiotics are recommended. Any medications that can cause vasoconstriction and promote ischemia should be withdrawn (ie, digitalis, glycosides, vasopressin, and diuretics). Marked colonic distention is treated with rectal tubes and nasogastric decompression if necessary. There is no role for anticoagulation or corticosteroids. Prognosis is favorable, and most patients improve within a few days and demonstrate clinical and radiologic resolution within 2 weeks.

Indications for surgery include peritoneal signs suggesting perforation, gangrenous colitis, massive bleeding, toxic megacolon, and recurrent sepsis. Long-term complications, including persistent recurrent colitis and colonic structures, are infrequent but may require resection of the affected colonic segment.

In contrast to small bowel ischemia, colonic ischemia is rarely life threatening. However, some reports suggest that ischemia of the right colon may have a worse prognosis compared with ischemia of other parts of the colon. Furthermore, the development of colonic ischemia in the setting of recent cardiovascular surgery also deserves special mention, as the natural history of colonic ischemia in these patients may be more severe. Prolonged colonic ischemia, such as can occur in patients with ruptured abdominal aortic aneurysms or prolonged aortic cross-clamp time, can lead to acute gangrenous colitis and transmural infarction of the colon. Although emergent operative intervention may be necessary in the setting of sepsis and peritoneal signs, most cases of colonic ischemia resolve with conservative management.