GI Consult: Mesenteric Ischemia Syndromes

Although mesenteric ischemia accounts for no more than 2% of hospitalizations for gastrointestinal conditions, it must be included in the initial differential diagnosis of abdominal pain, the authors say, because a timely diagnosis minimizes the risk of a disastrous bowel infarct. They explain how and why the several forms of mesenteric ischemia develop, when to suspect them, and how to investigate.

By David Tessler, DO, and Ronald Fogel, MD

The variable clinical presentation of mesenteric ischemia is a diagnostic dilemma for primary physicians. The nonspecific symptoms and the potential for catastrophic outcomes require the physician to be deliberately mindful of this diagnostic possibility and to perform the appropriate investigations in a timely fashion. Ischemic events can be classified by the rapidity of symptom onset, the degree of impairment of blood flow, and the region of the bowel affected. In this review, we will provide a summary of the clinical presentations, recommended diagnostic tests, and possible treatment options for the mesenteric ischemia syndromes (as outlined in the table below).

What causes acute mesenteric ischemia?

Acute mesenteric ischemia (AMI) is the clinical syndrome resulting from a decrease in blood flow to the small intestine, usually involving the circulation of the superior mesenteric artery (SMA). Emboli to the SMA are responsible for almost half of all cases of AMI. Emboli result from disruption of a thrombus in the left ventricle or atrium in the setting of atrial fibrillation, myocardial infarction, cardioversion, or cardiac catheterization. The middle colic artery is the vessel obstructed most frequently.

Thrombosis of the SMA causes 15% to 25% of cases of AMI. The obstruction is often located at the origin of the SMA. Risk factors for thrombosis are the same as those causing atherosclerosis in other vessels: hypercholesterolemia, hypertension, diabetes mellitus, and age. Hypercoagulable states, arterial aneurysms, dissections, and vasculitis are less common causes of SMA thrombosis. Thrombosis can also occur during a low-flow state in vessels with pre-existing stenotic lesions.

Nonocclusive mesenteric ischemia (NOMI), or mesenteric vasospasm in the absence of vascular occlusion, causes AMI in 20% to 30% of cases. As a result of systemic hypoperfusion, mesenteric vasospasm occurs to preserve cardiac and cerebral blood flow. The vasospasm may persist after the hypotension resolves, leading to ongoing intestinal ischemia. Causes of NOMI include myocardial infarction, aortic insufficiency, congestive heart failure, renal insufficiency, cardiac or intra-abdominal surgery, cardiopulmonary bypass, treatment with vasoconstrictive drugs such as digitalis, diuretics, and alpha-adrenergic agents, and use of cocaine.

Superior mesenteric venous thrombosis (SMVT) accounts for 5% of cases of AMI. The thrombosis results from a combination of low flow through the mesenteric vessels and a hypercoagulable state. Although some patients do not have an identifiable cause for the SMVT, many others have a definite precipitating etiology. Causes of mesenteric venous thrombosis include: primary hypercoagulable syndromes such as factor V Leiden mutation, protein C deficiency, antithrombin III deficiency, protein S deficiency, and anticardiolipin antibodies; hematologic disorders associated with thrombosis, such as polycythemia vera, thrombocytosis, and paroxysmal nocturnal hemoglobinuria; intra-abdominal inflammation as in pancreatitis, peritonitis, or inflammatory bowel disease; intra-abdominal surgery; and cirrhosis with portal hypertension.
 

What is the clinical presentation of AMI?

The classical presentation of AMI is severe periumbilical pain that is disproportionate to the findings on physical examination. This clinical picture, however, is often not seen. In practice, many patients initially complain of vague symptoms such as lower abdominal pain, abdominal distension, diarrhea, nausea with vomiting, or anorexia.

The duration and severity of the presenting symptoms depend on the cause of the vascular obstruction. Progression to severe symptoms tends to be faster in embolic disease than in the other ischemic syndromes because sudden vascular obstruction does not allow for the development of collateral circulation. Patients with AMI due to embolism often present to the physician after several hours of rapidly increasing pain. In contrast, SMA thrombosis occurs in vessels with pre-existing stenosis, allowing the development of a more extensive collateral system. Consequently, with this etiology, patients may have subtle symptoms at first and present to the emergency department only after pain has progressed for several days. Likewise, patients with SMVT often have had pain for days or even a week before seeing a physician.

Although most cases of abdominal pain are not due to AMI, mesenteric ischemia is not rare, being the cause of 1% to 2% of hospitalizations for gastrointestinal conditions. The reason for including AMI in the initial differential diagnosis is related to the dramatic increase in mortality with intestinal infarction. One study of patients with AMI found that mortality for those without intestinal infarction was less than 50% of that recorded for those who did have an infarcted bowel. Additionally, the probability of intestinal viability was inversely related to the duration of symptoms. All patients with symptoms of less than 12 hours' duration retained intestinal viability, but of those who were symptomatic for more than 24 hours before diagnosis, only 18% had intestinal viability.

For many patients, the abdominal pain of AMI cannot be distinguished from the other types of abdominal pain that bring patients to a physician or an emergency department. Therefore, the clinician must look for clues to suggest a vascular event. The diagnosis of SMA embolism should be considered for patients with sudden onset of abdominal pain and evidence of synchronous emboli to other organs. This clinical picture is observed in approximately 20% of patients with SMA emboli. The presence of acute abdominal pain in patients with cardiac disease, arrhythmias, or evidence of vascular disease requires that mesenteric ischemia be excluded. A history of dehydration or hypotension preceding the abdominal pain may be another clue to mesenteric ischemia.

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How does one evaluate a patient with suspected AMI?

The differential diagnosis of the sudden onset of abdominal pain is extensive. Perforated viscus, bowel obstruction, pancreatitis, and nephrolithiasis are diagnosed more frequently than AMI. Blood tests do not yield information useful in distinguishing among the possible diagnoses. Plain abdominal films can exclude other causes of abdominal pain such as viscus obstruction or perforation but are not helpful in the early diagnosis of intestinal ischemia. Thumbprinting (see image) is a nonspecific finding in mesenteric ischemia indicating interstitial edema with hemorrhage. Pneumoperitoneum, pneumatosis intestinalis, and gas in the portal vein may indicate infarcted bowel.

Radiographic evidence. The arrow indicates "thumbprinting" of the transverse colon. Note the accentuated focal thickening that indents the air of the bowel as if a thumb were pressing on the air column. This finding is not specific to ischemic disease; it also is reported in inflammatory conditions such as Clostridium difficile colitis and infiltrating neoplasms such as lymphoma.

Colonoscopy, abdominal ultrasonography, and barium radiography are not useful in the diagnostic workup of AMI. Barium enema is contraindicated if the diagnosis of AMI is being considered. The intraluminal barium can impede accurate visualization during angiography. Additionally, there is a risk of intraperitoneal leakage of barium if perforation is present.

Abdominal computed tomography (CT) scans are valuable to exclude some causes of abdominal pain from the differential diagnosis as well as to distinguish among the possible causes of AMI. The CT technique is not helpful in the diagnosis of embolic occlusions or NOMI but is the method of choice to diagnose SMVT. An American Gastroenterology Technical review states "that a contrast-enhanced CT scan should be the initial imaging study in patients with abdominal pain who have a history of deep venous thrombosis or thrombophlebitis or a family history of hypercoagulable state."

Doppler ultrasonography and magnetic resonance angiography are newer imaging techniques that have not yet been studied extensively. Their role in the investigation of patients with abdominal pain and suspected AMI remains to be determined.

Mesenteric angiography is the test of choice for the diagnosis of arterial causes of AMI. Angiography serves as a diagnostic test to identify emboli and thrombi, localize vascular obstructions, and characterize the collateral circulation. This test is the only way to diagnose NOMI before intestinal infarction occurs. Angiography is indicated in patients with suspected AMI who do not have signs of peritonitis. The primary physician must pay close attention to intravascular volume status before ordering the angiogram in these severely ill patients to prevent the renal complication of acute tubular necrosis. Exploratory surgery for patients presenting with signs of peritonitis should not be delayed for angiography.
 

What are the general principles of therapy?

Initially, the primary physician should focus on resuscitation of the patient, stabilization of cardiac function, and initiation of antibiotic therapy with broad-spectrum coverage. Medications that have vasoconstrictive effects should be discontinued. If there is evidence of peritonitis, a surgical consultation and laparotomy are indicated. A "second look" laparotomy, 24 to 48 hours after the first surgery, is performed by many surgeons when the viability of the nonresected bowel is in doubt.

For angiographically diagnosed SMA emboli, treatment options to restore intestinal blood flow include surgical revascularization, intra-arterial thrombolysis, intra-arterial vasodilation, and systemic anticoagulation. If peritonitis is present, surgical embolectomy with resection of infarcted bowel is indicated. In the absence of peritonitis, surgical embolectomy is the treatment of choice for major emboli. Thrombolytic therapy (streptokinase, urokinase, or recombinant tissue plasminogen activator) has been reported to be successful in individual cases and in small series of patients. Thrombolysis has a higher probability of success when performed within 12 hours of symptom onset. Following embolectomy, infusion of the vasodilator papaverine has been recommended by many investigators to prevent further ischemia due to vasospasm of the mesenteric arteries. Postoperative anticoagulation is used to prevent recurrence.

Surgical revascularization is indicated for treatment of acute mesenteric thrombosis. Thrombectomy alone does not provide long-term relief because thrombogenic atherosclerotic plaques remain in the vessel. Although successful therapy with thrombolytic infusion and angioplasty has been reported in a subset of patients, this approach is not yet the standard of care. Patients with NOMI but without intestinal infarction have been successfully treated with intra-arterial infusion of papaverine. Anticoagulation alone is the mainstay of treatment for patients with SMVT who do not have evidence of infarcted bowel.
 

What is intestinal angina?

Intestinal angina, also called chronic mesenteric ischemia, is a clinical syndrome of reduced mesenteric blood flow that interferes with physiologic function but does not cause infarction. In contrast to the reduction in SMA blood flow that causes AMI, mesenteric angina is the result of intestinal hypoperfusion through two of the three major vessels supplying the small intestine: the SMA, the celiac artery, and the inferior mesenteric artery. Diffuse mesenteric atherosclerosis causes high-grade stenoses at the origin of the vessels, reducing blood flow to the tissue. Risk factors for intestinal angina include atherosclerosis, hypertension, diabetes, and cigarette smoking.

Patients with intestinal angina complain of periumbilical abdominal pain that starts approximately 30 minutes after eating and lasts for one to two hours. The patient may recognize the relationship between eating and abdominal pain, resulting in a fear of eating and weight loss. Some patients, however, will present with anorexia and weight loss without complaints of abdominal pain. In this group of patients, the diagnosis may be delayed while an extensive investigation is undertaken for occult malignancy.

Other symptoms of intestinal angina include diarrhea, nausea, and vomiting. These symptoms can accompany postprandial abdominal pain but occasionally may be the only symptoms of ischemia. Edema and muscle wasting as a result of malnutrition are unusual presentations. Finally, patients with undiagnosed mesenteric angina may present with infarction of the bowel due to thrombosis of one of the major vessels. In summary, chronic mesenteric ischemia must be considered in patients with a variety of abdominal complaints, if there is a history suggestive of vascular problems.

In view of the nonspecific symptoms of mesenteric angina as well as the discomfort and morbidity associated with angiography (the current gold standard to diagnose mesenteric angina), physicians will often undertake an extensive series of endoscopic and radiologic investigations to exclude other possible causes for the symptoms. The primary physician must be astute and not attribute the symptoms of ischemia to trivial abnormalities that may be found during this workup.

The diagnosis of mesenteric angina is made in patients with symptoms consistent with the diagnosis and high-grade stenoses in at least two mesenteric vessels. Angiography also provides information regarding the circulation distal to the stenosis, information important to the vascular surgeon considering revascularization.

Recently, investigators have reported that mesenteric duplex ultrasonography has a sensitivity exceeding 90% for the diagnosis of significant proximal stenosis. Nevertheless, it is currently recommended that the diagnosis of mesenteric vessel stenosis made by ultrasonography be verified by angiography.

Surgical revascularization has been the therapy of choice for mesenteric angina, but percutaneous transluminal mesenteric angioplasty is gaining popularity as an alternative treatment option. Success rates are similar (75% to 95%), although recurrence rates are higher with angioplasty (10% to 67%). Angioplasty may be the preferred treatment for patients who are not surgical candidates. In the future, angioplasty with vascular stenting may be the treatment of choice for all patients with mesenteric angina.

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What is ischemic colitis?

Ischemic colitis is the most common form of mesenteric ischemia, responsible for almost 50% of cases with a mesenteric ischemia diagnosis. The clinical syndromes result from a reduction in blood flow through the inferior mesenteric artery and the colonic collaterals of the SMA. Presentations of ischemic colitis include reversible ischemia with submucosal and intramural hemorrhage, transient colitis, stricture formation, and fulminant colitis. Generalized atherosclerosis and low-flow states predispose to colonic ischemia. Sepsis, cardiogenic shock, cardiopulmonary bypass surgery, and hypovolemia due to pancreatitis, diarrhea, and hemorrhage can reduce blood flow to the colon. Colonic obstruction with increased intramural pressures can also decrease colonic blood flow. Among young patients with ischemic colitis, conditions contributing to the ischemia include hypercoagulable states, vasculitis, sickle cell disease, drugs such as oral contraceptives, and illicit agents such as cocaine. Finally, ischemic colitis has been reported as a complication of vigorous exercise in athletes who run in marathons.

Although any area of the colon may be ischemic, the left colon is affected in 75% of cases. In particular, the splenic flexure and sigmoid colon are frequently involved. The rectum is an unusual location for colonic ischemia.

Patients with ischemic colitis frequently present with red or maroon blood mixed with soft or liquid stool and mild, crampy, left-sided abdominal pain of acute onset. The bleeding tends to be mild and blood transfusions are rarely necessary. Other presenting symptoms may include diarrhea, nausea, vomiting, and anorexia. Peritonitis is unusual.

Rarely, patients with colonic ischemia present with constipation or with a complaint of thin stool. In these cases, chronic ischemia has caused a stricture secondary to fibrosis.

Plain films of the abdomen do not provide any specific information to diagnose ischemic colitis but can exclude viscus perforation. Thumbprinting can be detected. Colonoscopy is the preferred test for the diagnosis of ischemic colitis. Evidence favoring the diagnosis of ischemic colitis includes segmental distribution of injury, sharp demarcation between injured and normal mucosa, and rectal sparing. Biopsies of the mucosa usually yield only nonspecific findings of submucosal hemorrhage and vascular congestion. Biopsies are indicated, however, when examination of the mucosa reveals inflammation that resembles ulcerative colitis or Crohn's disease or when an ulcer or stricture suggests colorectal cancer. Caution is necessary during colonoscopic evaluation. The endoscopist must remember that over-distension of the colon during the procedure can further impair colonic blood flow and that biopsy may cause perforation if full-thickness ischemia is present.

Barium enema does not provide specific findings to diagnose ischemia. Abdominal CT scans are useful to exclude other diseases that could be causing the symptoms. Mesenteric angiography is not indicated to diagnose ischemic colitis.

In general, therapy for patients with ischemic colitis is supportive. Most patients receive fluid resuscitation and bowel rest. The majority of patients with ischemic colitis improve within 24 to 48 hours of symptom onset. Although older studies suggested that antibiotics were beneficial for patients with colonic ischemia, there is no recent clinical evidence to support the use of this therapy.The indications for surgery include peritonitis, massive bleeding, or clinical deterioration despite adequate therapy.

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