Acute mesenteric ischemia Authors David A Tendler, MD J Thomas LaMont, MD Section Editor Lawrence S Friedman, MD Deputy Editor Kathryn

A Collins, MD, PhD, FACS

All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Fev 2012. | This topic last updated: Ago 19, 2009.

INTRODUCTION Mesenteric ischemia is caused by a reduction in intestinal blood flow, which most commonly arises from occlusion, vasospasm, and/or hypoperfusion of the mesenteric vasculature. The clinical consequences can be catastrophic, including sepsis, bowel infarction, and death, making rapid diagnosis and treatment imperative. Intestinal ischemia can be divided into acute and chronic, based upon the rapidity and the degree to which blood flow is compromised.

Acute mesenteric ischemia refers to the sudden onset of intestinal hypoperfusion, which can be due to occlusive or nonocclusive obstruction of arterial or venous blood flow. Occlusive arterial obstruction is most commonly due to emboli or thrombosis of mesenteric arteries, while occlusive venous obstruction is most commonly due to thrombosis or segmental strangulation. Nonocclusive arterial hypoperfusion is most commonly due to primary splanchnic vasoconstriction. Chronic mesenteric ischemia (also called intestinal angina) refers to episodic or constant intestinal hypoperfusion, which usually develops in patients with mesenteric atherosclerotic disease. Acute mesenteric ischemia involving the small intestine will be reviewed here. Chronic mesenteric small intestinal ischemia and colonic ischemia are discussed separately. (See "Chronic mesenteric ischemia" and "Colonic ischemia".) The American Gastroenterological Association (AGA) guideline for intestinal ischemia [1], as well as other AGA guidelines, can be accessed through the AGA web site at http://www.gastro.org/practice/medical-position-statements. VASCULAR SUPPLY OF THE INTESTINES An extensive collateral circulation exists to protect the intestines from transient periods of inadequate perfusion. However, prolonged reduction in splanchnic blood flow leads to vasoconstriction in the affected vascular bed, which can eventually reduce collateral blood flow [2,3]. The likelihood of developing intestinal ischemia depends upon the adequacy of systemic perfusion and collateral circulation, the number and caliber of splanchnic vessels that are affected, and the duration of the ischemic insult. Celiac axis The celiac artery arises from the anterior aspect of the abdominal aorta and typically branches into the common hepatic, splenic, and left gastric arteries. The common hepatic artery usually gives rise to the gastroduodenal artery (in approximately 75 percent of people), which in turn branches off into the right gastroepiploic artery and the anterior and posterior superior pancreaticoduodenal arteries. The right gastroepiploic artery joins with the left gastroepiploic artery, which emanates from the splenic artery in 90 percent of patients. The right gastric artery branches from the hepatic artery and anastomoses with the left gastric artery along the lesser curvature of the stomach. Because of its highly redundant blood supply, gastric ischemia is rare. Superior mesenteric artery The superior mesenteric artery (SMA) arises approximately 1 cm below the celiac artery and runs inferiorly toward the cecum, terminating as the ileocolic artery. Along the way, it gives rise to the inferior pancreaticoduodenal artery, several jejunal and ileal branches, the middle colic artery, and the right colic artery. As a general rule, the middle colic artery arises from the proximal SMA and supplies the proximal to mid-transverse colon. However, it occasionally provides the predominant blood flow to the splenic flexure. The right colic artery arises either from a common trunk with, or just below, the middle colic artery, and supplies blood to the mid-distal ascending colon. The ileocolic artery supplies the distal ileum, cecum, and proximal ascending colon. Inferior mesenteric artery The inferior mesenteric artery arises approximately 6 to 7 cm below the SMA. The IMA gives rise to the left colic artery, the sigmoid arteries, and the hemorrhoidal arteries. It is largely responsible for blood supply from the distal transverse colon to the rectum. Collateral circulation The splanchnic circulation is characterized by a vast network of collateral blood vessels, which impart redundancy, and as a result, substantial protection from ischemia or infarction in settings of segmental vascular occlusion. The major collateral connections are:

The celiac axis and the SMA, which communicate principally through the junction of the superior and inferior pancreaticoduodenal arteries. Several smaller conduits have also been described. The SMA and IMA, which communicate through several pathways. The middle colic and left colic arteries primarily anastomose through the marginal artery of Drummond, which runs along the mesentery of the splenic flexure of the colon and the arc of Riolan. Collateralization between the IMA and systemic circulation, which occurs in the rectum, as the superior rectal (hemorrhoidal) vessels merge with the middle rectal vessels from the internal iliac arteries. MESENTERIC PHYSIOLOGY Changes in the resistance of mesenteric arterioles account for wide fluctuations in splanchnic blood flow, which can range from 10 to 35 percent of cardiac output. Numerous control mechanisms contribute to the regulation of mesenteric vascular tone and are responsive to varying conditions such as the postprandial state or systemic hypotension [4]. Intrinsic autoregulation of blood flow by the splanchnic vessels is thought to occur in response to acute reductions in perfusion

pressure. Proposed mechanisms that result in the preservation of tissue perfusion include direct arteriolar smooth muscle relaxation and a metabolic response to adenosine and other metabolites of mucosal ischemia [5]. Neural and hormonal mechanisms also contribute to the extrinsic control of intestinal blood flow. These include the sympathetic nervous system, the renin-angiotensin axis, and vasopressin, which is released from the pituitary gland. An understanding of these mechanisms has led to the therapeutic use of vasopressin, which, by causing mesenteric vasoconstriction and venorelaxation, is effective in reducing portal venous pressures in patients with bleeding from portal hypertension. (See "General principles of the management of variceal hemorrhage".) Response to ischemia Ischemic injury to the intestine develops when there is insufficient delivery of oxygen and nutrients required for cellular metabolism. The intestine is able to compensate for approximately a 75 percent acute reduction in mesenteric blood flow for up to 12 hours without substantial injury, in part because of increased oxygen extraction [6]. Collateral circulation opens almost immediately after occlusion of a major vessel. However, after several hours, progressive vasoconstriction develops in the obstructed bed, increasing its pressure and thereby reducing collateral flow. Vasoconstriction may persist even after blood flow has been restored leading to continued intestinal ischemia and providing the rationale for therapeutic infusion of papaverine (a vasodilator) during angiography (see 'Diagnosis' below). Ischemic damage is caused both by hypoxia and reperfusion injury. Most of the damage is due to reperfusion injury after a brief period of ischemia while the detrimental effects of hypoxia predominate with longer periods of ischemia [7]. ACUTE MESENTERIC ISCHEMIA Acute insufficiency of mesenteric arterial blood flow accounts for 60 to 70 percent of cases of mesenteric ischemia, and results in mortality rates exceeding 60 percent [2]. Specific risk factors include advanced age, atherosclerosis, low cardiac output states, cardiac arrhythmias, severe cardiac valvular disease, recent myocardial infarction, and intra-abdominal malignancy [2]. The incidence of acute mesenteric ischemia appears to be rising, which may be due in part to an increased awareness of the disorder among clinicians and an aging population with severe cardiovascular and/or systemic disease. Another contributing factor may be the increased use of intensive care units, which has resulted in the prolonged survival of critically ill patients, enabling them to develop mesenteric ischemia as a late consequence of their illnesses. In younger patients without cardiovascular disease, mesenteric venous thrombosis is the major cause of acute ischemia of the small bowel. The four major causes of acute mesenteric ischemia are [3,8]:

Superior mesenteric artery embolism (50 percent) Superior mesenteric artery thrombosis (15 to 25 percent) Mesenteric venous thrombosis (5 percent) Nonocclusive ischemia (20 to 30 percent) Acute mesenteric ischemia may also be observed less frequently in the setting of an underlying vasculitis. (See "Gastrointestinal manifestations of vasculitis".) Mesenteric arterial embolism Embolism to the mesenteric arteries is most frequently due to dislodged thrombus from the left atrium, left ventricle, or cardiac valves. (See "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation".) The SMA is anatomically most susceptible to embolism due to its large caliber and narrow take-off angle from the aorta. The IMA is rarely affected due to its small caliber [8]. The embolus usually lodges 3 to 10 cm distal to the origin of the SMA, in a tapered segment distal to the take off of the middle colic artery. Approximately 15 percent of emboli lodge in the origin of the SMA [2]. Over 20 percent of acute mesenteric emboli are multiple. Concomitant arteriolar vasoconstriction usually occurs, further impairing splanchnic blood flow and exacerbating the ischemia. The middle segment of the jejunum is most often involved in the ischemic process as it is most distant from the collateral circulation of the celiac and inferior mesenteric arteries. Mesenteric arterial thrombosis Acute thrombosis of the mesenteric circulation usually occurs as a superimposed phenomenon in patients with a history of chronic intestinal ischemia from progressive atherosclerotic stenoses. It can also occur in the setting of abdominal trauma or infection. There does not appear to be a significant association between inherited coagulation defects and mesenteric arterial thrombosis [9,10]. Thrombosis of the SMA or celiac axis usually occurs at the origin of the vessel, and involves at least two major splanchnic arteries, which may complicate attempts at revascularization [11]. Mesenteric venous thrombosis Risk factors for the development of mesenteric venous thrombosis include hypercoagulable states, portal hypertension, abdominal infections, blunt abdominal trauma, pancreatitis, splenectomy, and malignancy in the portal region. In a review of 51 patients, the highest incidence was in patients ages 70 to 79 [12]. Intestinal ischemia following mesenteric venous thrombosis is due to the resistance in mesenteric venous blood flow, which causes profound bowel wall edema, fluid efflux into the bowel lumen with resulting systemic hypotension, and an increase in blood viscosity. As a result, arterial flow is diminished, which ultimately leads to submucosal hemorrhage and bowel infarction [2]. Inherited hypercoagulable states Up to 75 percent of patients with mesenteric venous thrombosis have an inherited thrombotic disorder [12-14]. However, the true frequency of these disorders in patients with mesenteric venous thrombosis is difficult to estimate since most studies included patients with all forms of deep vein thrombosis. One study suggested that an acquired or inherited hypercoagulable state was more likely in patients with isolated mesenteric vein thrombosis compared with those with concomitant involvement of the portal or splenic veins [15]. The available data suggest that the most common disorder is the factor V Leiden mutation (causing resistance to activated protein C), which is present in 20 to 40 percent of patients [10]. Resistance to activated protein C also occurs from mutations other than the factor V Leiden mutation in approximately 10 percent of patients [16,17], and is an independent risk factor for venous thromboembolism [17,18]. Thus,

phenotypic evaluation for activated protein C resistance should be considered in patients with venous thromboses. (See "Activated protein C resistance and factor V Leiden".) Mutation of the prothrombin gene has also been associated with an increased risk for thrombotic events [19]. This mutation, which leads to higher plasma prothrombin levels, occurs in approximately 8 percent of individuals with a history of venous thrombosis, and in 2 percent of healthy controls, making it one of the more common causes of inherited thrombophilia [20]. In a small study, this mutation was found in 40 percent of patients with idiopathic portal vein thrombosis [21]. Further studies will be necessary to delineate the significance of these mutations in patients with thrombosis of the mesenteric veins. (See "Prothrombin gene mutation".) In addition to mutations of coagulation proteins, deficiencies of naturally occurring anticoagulant proteins, protein S, protein C, and antithrombin (AT) account for approximately 8 to 10 percent, while antiphospholipid antibodies are present in approximately 4 percent of patients [9,10,16,22]. Acquired hypercoagulable states A number of conditions are associated with acquired forms of hypercoagulability. Of these, the most common that are associated with mesenteric venous thrombosis are paroxysmal nocturnal hemoglobinuria and the myeloproliferative syndromes. (See "Overview of the causes of venous thrombosis", section on 'Myeloproliferative neoplasms and PNH'.) Prognosis Few studies have described the long-term outcome in patients who developed mesenteric venous thrombosis. One of the largest series included 60 patients with chronic portomesenteric or portosplenomesenteric venous thrombosis who were followed for a median of 3.5 years [23]. Overall survival at one and five years were 82 and 78 percent, respectively. These values were 86 and 82 percent, respectively, after excluding patients with an underlying malignancy. Treatment with beta blockers and anticoagulation were associated with improved survival. Nonocclusive mesenteric ischemia Nonocclusive mesenteric ischemia (NOMI) is thought to occur as a result of splanchnic hypoperfusion and vasoconstriction [24]. Similar to mesenteric arterial thrombosis, nonocclusive mesenteric ischemia tends to develop in patients with significant atherosclerotic vascular disease. A typical patient is an elderly man or woman with cardiovascular disease who has a life-threatening complication (such as a myocardial infarction or congestive heart failure) and is being treated with drugs known to reduce intestinal perfusion (such as diuretics). Other common inciting events include aortic insufficiency, sepsis, cardiac arrhythmias, and administration of medications such as digoxin and alpha-adrenergic agonists. Several cases of nonocclusive mesenteric ischemia resulting from cocaine use have also been described [20,25]. There are also several reports of NOMI occurring in patients following cardiac surgery [26,27] and dialysis [28]. The risk for developing NOMI following cardiopulmonary bypass is greatest in those with long aortic cross-clamp times or for those who require inotropic drugs [27]. The pathogenesis of NOMI is related to mesenteric vasospasm, which is a homeostatic mechanism that functions to maintain cardiac and cerebral blood flow at the expense of the splanchnic and peripheral circulation. Vasopressin and angiotensin are probably the neurohormonal mediators of this phenomenon. The villus tips are most susceptible to injury because of their relatively high oxygen requirement. NOMI accounts for 20 to 30 percent of patients with acute mesenteric ischemia, which is approximately a 50 percent decline since the 1970s [11]. The decline has been attributed to the widespread use of invasive hemodynamic monitoring in intensive care units, coupled with the prompt correction of hypotension, and the use of systemic vasodilators in cardiac failure. Despite the decline in its incidence, when it occurs NOMI results in mortality of nearly 70 percent of cases, because of the difficulty in making the diagnosis and reversing the ischemia once it has started [29]. The severity and location of the abdominal pain that accompanies NOMI is usually more variable than the classic severe pain of acute occlusive mesenteric ischemia. Thus, a high index of suspicion in elderly patients with risk factors for NOMI is imperative for making a prompt diagnosis. CLINICAL MANIFESTATIONS Patients with acute mesenteric ischemia (AMI) have been classically described as having the rapid onset of severe periumbilical abdominal pain, which is often out of proportion to findings on physical examination. Nausea and vomiting are also common. Sudden pain associated with minimal abdominal signs and forceful bowel evacuation in a patient with risk factors for acute mesenteric ischemia should greatly heighten suspicion for the diagnosis. The presentation may be more insidious with mesenteric vein thrombosis in whom symptoms may have been present for weeks to months (typically 5 to 14 days) before diagnosis [2,30]. About one-half of patients have nausea and vomiting. Nonspecific abdominal pain may be the only feature in patients with a subacute presentation while those with chronic mesenteric ischemia may present with bleeding from esophageal or gastric varices due to concomitant portal or splenic vein thrombosis. Abdominal pain is absent in up to 25 percent of patients with nonocclusive ischemia in whom the clinical picture may be overshadowed by precipitating disorders including hypotension, congestive heart failure, hypovolemia, and cardiac arrhythmias. Several features of the pain and its presentation may also provide clues for distinguishing small bowel from colonic ischemia (table 1):

Severe pain is more likely with acute mesenteric ischemia involving the small bowel compared with mesenteric ischemia involving the colon, in which extreme pain is usually not as prominent a feature.

In patients with small bowel obstruction leading to ischemia, pain often precedes vomiting. The onset of pain is sudden when ischemia is caused by embolic disease. In contrast, the pain may occur more insidiously (hours to days) in patients with thrombotic causes, vasculitis, or nonocclusive ischemia. Lower abdominal pain associated with hematochezia is more likely with colonic ischemia. Abdominal examination may be normal initially or reveal only abdominal distension or occult blood in the stool. Signs of peritoneal inflammation, such as rebound tenderness and guarding, are absent. However, as bowel ischemia progresses and transmural bowel infarction develops, the abdomen becomes grossly distended, bowel sounds become absent, and peritoneal signs develop. A feculent odor to the breath may also be appreciated. Mental status changes are reported to occur in approximately one-third of elderly patients with AMI [31]. A careful general physical examination should be performed to look for signs of an underlying vasculitis. DIAGNOSIS The diagnosis of AMI depends upon a high clinical suspicion, especially in patients with known risk factors (such as atrial fibrillation, congestive heart failure, peripheral vascular disease, or a history of hypercoagulability). A careful review of the patient's personal and family history is important; as a personal history of a prior embolic event is present in approximately one-third of patients with acute embolic mesenteric ischemia, while a personal or familial history of a deep vein thrombosis or pulmonary embolism is present in about one-half of patients with acute mesenteric venous thrombosis [32]. In addition, patients with acute mesenteric thrombosis frequently had antecedent symptoms of chronic mesenteric ischemia including chronic postprandial abdominal pain, aversion to eating, and weight loss. Rapid diagnosis is essential to prevent the catastrophic events associated with intestinal infarction [33]. However, early signs and symptoms of mesenteric ischemia are nonspecific, and definitive diagnosis often requires invasive testing, exposing the patients who typically have several comorbidities to risk. As a result, the diagnosis is often delayed. (See "Differential diagnosis of abdominal pain in adults".) Our approach is generally consistent with a guideline proposed by the American Gastroenterological Association (algorithm 1AE). The AGA guideline for intestinal ischemia [1], as well as other AGA guidelines, can be accessed through the AGA web site at http://www.gastro.org/practice/medical-position-statements. Patients suspected of having AMI should be resuscitated (including measures aimed at relieving acute congestive heart failure and hypotension, correction of hypovolemia and cardiac arrhythmias) after which plain films and/or a CT scan should be considered. These tests do not exclude mesenteric ischemia but may identify whether it has progressed irreversibly while also helping to exclude other causes of abdominal pain. CT may be particularly valuable when mesenteric vein thrombosis is being considered. However, patients in whom there is strong clinical suspicion should proceed directly to angiography without delaying for a CT scan. If no alternative diagnosis is established and the clinical setting and radiographic findings do not warrant immediate laparotomy, patients should expeditiously undergo selective angiography of the SMA. Angiography is important even if surgery is planned since it can not only identify the site of vascular compromise but also can be used to relieve mesenteric vasoconstriction with infusion of papaverine. Improvement in mesenteric vasoconstriction is essential for treatment of emboli, thromboses, and nonocclusive ischemia. Laboratory studies Laboratory studies are nonspecific; while abnormal laboratory values may be helpful in bolstering suspicion for AMI, normal laboratory values do not exclude AMI and do not justify delaying angiography when clinical suspicion for AMI exists. Findings may include a marked leukocytosis with a predominance of immature white blood cells, an elevated hematocrit consistent with hemoconcentration, and a metabolic acidosis. A useful clinical guideline is that any patient with acute abdominal pain and metabolic acidosis has intestinal ischemia until proven otherwise. Many individual laboratory values have been examined to ascertain their utility in diagnosing mesenteric ischemia or infarction [34]. Unfortunately, most abnormalities have been found to arise once the ischemic insult has progressed to bowel necrosis.

One study suggested that elevation in the serum lactate was 100 percent sensitive but only 42 percent specific for intestinal ischemia/infarction [35]. The specificity of an elevated serum lactate level does improve significantly when conditions such as shock, diabetic ketoacidosis, renal and hepatic failure can be excluded [35]. Another study demonstrated elevated lactate levels in 17 of 22 patients with bowel infarction, yielding a sensitivity of 77 percent [36]. Elevated serum amylase levels have been observed in about one-half of patients with intestinal ischemia [37,38], while phosphate elevations were found in 80 percent [39]. Normal D-dimer levels may help to exclude acute intestinal ischemia but elevated levels are less useful for its diagnosis [40]. Animal models of acute intestinal ischemia have demonstrated an increase in D-dimer levels beginning 30 minutes after the ischemic event [41]. However, elevated levels can also be seen in a variety of conditions such as in patients with acute pancreatitis and those with an abdominal aortic aneurysm [42,43]. Experimental tests Measurement of serum alpha-glutathione S-transferase (alpha-GST) and intestinal fatty acid-binding protein (I-FABP) has been evaluated in a few studies [38,44]. Alpha-GST appears to have a cytoprotective role against oxidative injury. An elevated alpha-GST had a 72 percent sensitivity and 77 percent specificity for diagnosing AMI, but could not distinguish between ischemia and infarction [38]. Overall accuracy was 74 percent, compared to an accuracy of 47 to 69 percent for conventional laboratories, consisting of lactate, pH, amylase, base excess, and white blood cell count. The negative predictive value of alpha-GST was 90 percent when combined with serum lactate and 100 percent when combined with the white blood cell count. Similarly, patients with ischemic bowel disease, particularly those with mesenteric infarction, were found to have significant elevations in I-FABP [44]. In the ischemia-reperfusion model of intestinal ischemia, whole blood platelet aggregation, an indicator of platelet function, was significantly lower than in control groups and correlated well with small intestinal histological damage [45]. Another animal model demonstrated that serum levels of D(-)-lactate, a product of bacterial fermentation, was significantly elevated

following an ischemia-reperfusion insult and also correlated with intestinal histologic injury [46]. Studies are needed to validate these findings in humans.

A cobalt-albumin binding assay (CABA) was assessed in 26 patients who were scheduled for laparotomy for clinical features consistent with AMI and/or bowel obstruction [47]. Postoperatively, 12 patients were diagnosed with AMI, all of whom had significantly higher CABA levels than those who did not have AMI. The sensitivity and specificity were 100 and 86 percent, respectively. A significant increase in the levels of ischemia-modified albumin (IMA) were found in seven patients with acute thromboembolic SMA occlusions, compared with healthy controls [48]. Larger studies will be necessary to validate these findings. Radiographic studies Mesenteric angiography remains the gold standard diagnostic study for acute arterial ischemia. Early and liberal implementation of angiography has been the major factor for the decline in the mortality of patients with acute mesenteric ischemia over the past 30 years [11]. Both anteroposterior and lateral views are needed for adequate visualization of the mesenteric vasculature. The origins of the celiac axis and SMA are visualized only with the lateral view, while the distal celiac axis and remainder of the SMA are assessed best with anteroposterior projections. Angiography is relatively less sensitive for superior mesenteric vein thrombosis [49]. In patients with NOMI, arteriography can demonstrate areas of narrowing and irregularity in major branches, decreased or absent flow in the smaller vessels, and an absent submucosal "blush." Mesenteric venous thrombosis may be diagnosed during the venous phase of the exam by the presence of venous filling defects or absent flow. In addition, resistance to venous flow permits visualization of refluxed contrast into the aorta. In severe cases, contrast extravasation into the bowel lumen may be seen, indicating active bleeding. Isolated mesenteric vein thrombosis may be more difficult to diagnose compared with mesenteric vein thrombosis that also involves the portal or splenic veins [15]. The diagnosis of mesenteric ischemia may also be suggested on several less invasive tests. Plain abdominal x-rays are relatively nonspecific and may be completely normal in more than 25 percent of patients [2]. Suggestive findings include the presence of an ileus with distended loops of bowel, bowel wall thickening (particularly prominent in acute mesenteric venous thrombosis), and/or pneumatosis intestinalis (picture 1). The latter may be observed in patients with advanced ischemia. Intraluminal barium studies are contraindicated since they interfere with visualization on angiography and offer little information. Doppler-flow ultrasonography can visualize stenoses or occlusions in the celiac or superior mesenteric arteries. However the test is often technically limited by the presence of air-filled loops of distended bowel. In addition, its sensitivity is limited for detecting more distal emboli or in the assessment of NOMI. Computerized tomography (CT scan) of the abdomen may show focal or segmental bowel wall thickening or intestinal pneumatosis with portal vein gas (picture 2). Mesenteric arterial occlusions can be demonstrated as lack of enhancement of the arterial vasculature with timed intravenous contrast injections. The accuracy of CT was evaluated in a study comparing CT findings in 39 patients who had surgically proven AMI with 24 controls in whom suspected acute mesenteric ischemia was disproved at surgery [50]. The finding of either arterial or venous thrombosis, intramural gas, portal venous gas, focal lack of bowel-wall enhancement, or liver or splenic infarcts had a sensitivity and specificity of 64 and 92 percent, respectively. The presence of just one of several imaging criteria was needed to be a positive study; thus, the predictive value of traditional spiral CT imaging in the clinical setting may not be as high as that seen in research settings. In other studies, the sensitivity of CT for the diagnosis of mesenteric venous thrombosis was approximately 90 percent [13]. Diagnosis was made by the failure to opacify the mesenteric veins with intravenous contrast. The presence of pneumatosis intestinalis on CT does not necessarily indicate that transmural infarction has occurred; transmural infarction is more likely in patients with pneumatosis and portomesenteric venous gas [51]. Magnetic resonance angiography (MRA) and the newest generation of CT angiography, known as multidetector row CT (MDCT), can provide much more detailed information about the mesenteric vessels and the small bowel than their predecessors [52-60]. Initial experience suggests MRA may be highly sensitive for the diagnosis of mesenteric venous thrombosis, although CT is still preferred because of its lower costs, wide availability, and excellent sensitivity for diagnosing SMV thrombosis [54,56]. Emerging experience suggests that MDCT-angiography has a high degree of accuracy for diagnosing occlusive and nonocclusive acute mesenteric ischemia. An illustrative study included 91 consecutive patients with suspected acute mesenteric ischemia in which MDCT-angiography correctly diagnosed ischemia in 16 of 18 patients [61]. In total, there were two false positives and two false negative CT results while overall accuracy was 96 percent. More data comparing these modalities to conventional angiography are needed, especially to understand whether these studies can accurately detect the presence of small thromboemboli, early, reversible ischemia, or nonocclusive ischemia [59]. Angiography is still recommended if there is a strong clinical suspicion for these entities. TREATMENT The goal of treatment of patients with AMI is to restore intestinal blood flow as rapidly as possible. Initial management should include aggressive hemodynamic monitoring and support, correction of metabolic acidosis, initiation of broad spectrum antibiotics, and placement of a nasogastric tube for gastric decompression. Vasoconstricting agents and digitalis should be avoided if possible since they can exacerbate mesenteric ischemia. If vasopressors are required, dobutamine, low-dose dopamine, or milrinone are preferred since they have less of an effect on mesenteric perfusion compared with other vasopressor agents. (See "Use of vasopressors and inotropes".) Systemic anticoagulation should be administered to prevent thrombus formation or propagation unless patients are actively bleeding. Anticoagulation is typically reinstituted after surgery to prevent new thrombus formation [3].

Surgery should not be delayed in patients suspected of having intestinal infraction or perforation based upon clinical, radiographic, or laboratory parameters. In other patients and in those in whom the diagnosis is unclear, the early performance of mesenteric angiography is imperative since it permits accurate diagnosis and possibly therapeutic intervention. Hemodynamic stabilization should be achieved prior to the study since angiography will demonstrate mesenteric vasoconstriction, even in the absence of mesenteric ischemia, in the setting of hypotension or hypovolemia. The benefit of early angiography was demonstrated in a series in which a 67 percent survival rate was observed in patients with acute SMA embolism when a protocol involving prompt angiography was initiated within 12 hours of the suspected event [11]. This is a vast improvement from the 70 percent mortality rate observed in the late 1960s. Therapeutic options during angiography include the administration of intra-arterial vasodilators or thrombolytic agents, angioplasty, placement of a vascular stent, and embolectomy depending upon the cause of ischemia and the anatomy of the obstruction. As a general rule, intra-arterial papaverine is beneficial in the management of occlusive and nonocclusive acute mesenteric ischemia since vasoconstriction occurs in response to diminished SMA blood flow and can persist if not corrected within the first few hours [11,29,62]. Papaverine can be safely infused for up to five days. Treatment of specific types of mesenteric ischemia will be discussed in the following sections. Mesenteric arterial embolism The traditional treatment of mesenteric arterial embolism has been early surgical laparotomy with embolectomy. Surgical embolectomy is accomplished by performing an arteriotomy distal to the embolism and then advancing a balloon-tipped embolectomy catheter. Palpation for SMA pulses is performed and the small bowel is carefully examined for areas of persistent ischemia, which are resected. Intraoperative duplex ultrasonography can assist in identifying persistently ischemic segments [3]. Postoperative administration of papaverine can attenuate associated vasospasm. A "secondlook" laparotomy within the next 24 to 48 hours may be necessary to resect additional ischemic or gangrenous bowel. A less well established approach is local infusion of thrombolytic therapy, which has been successful in a number of reports [6365]. Thrombolytic therapy should only be considered in patients who can undergo angiography within eight hours of the onset of abdominal pain and who do not have clinical evidence of bowel infarction or other contraindications to thrombolytic therapy. (See "Fibrinolytic (thrombolytic) agents in acute ST elevation myocardial infarction: Therapeutic use" and "Fibrinolytic (thrombolytic) therapy in acute pulmonary embolism and lower extremity deep vein thrombosis".) A detailed review of 20 case reports and seven small series of thrombolytic therapy for acute SMA occlusion reported angiographic resolution of the occlusion in 43 of 48 patients (90 percent), most of whom were treated with infusions of urokinase. Eighteen patients required additional surgical intervention, with overall 30-day survival in 43 patients [66]. Concomitant infusion of papaverine has been advocated [2]. Surgical exploration is mandatory in patients who do not demonstrate clot lysis within four hours or develop evidence of progressive ischemia. Despite success in case series, the longterm reocclusion rate after thrombolytic therapy has not been well studied. Long-term management is aimed at the prevention of future embolic events, typically with the use of warfarin [67]. Mesenteric arterial thrombosis Treatment of patients with acute mesenteric artery thrombosis is principally surgical. Thrombectomy alone is unlikely to offer a durable solution, due to the persistence of thrombogenic atherosclerotic plaques. As a result, various revascularization techniques, in conjunction with thrombectomy, and resection of non-viable segments have been advocated. Mesenteric artery reconstruction is associated with good long-term patency rates, as well as symptom-free survival (79 percent and 77 percent, respectively), notwithstanding a high perioperative mortality rate of 52 percent [68]. Successful endovascular approaches with stenting have also been reported [69-71]. On the other hand, observation while on heparin anticoagulation may be justified in patients without peritoneal signs who have angiographic evidence of good collateral blood flow. The use of antiplatelet agents in the perioperative period has not been well evaluated, but aspirin administration may be justified in this setting if the risk of progressive ischemia appears to be greater than the risk of bleeding. If peritoneal signs are present, collateralization is insufficient, or SMA filling is poor, continuous papaverine infusion and laparotomy is warranted. After recovery, antiplatelet agents such as aspirin may reduce the risk of recurrent mesenteric ischemia [67]. Mesenteric venous thrombosis Standard initial treatment for acute mesenteric venous thrombosis includes heparin anticoagulation and resection of infarcted bowel [72]. Anticoagulation with heparin can be given even in patients who have gastrointestinal bleeding if the bleeding risk is considered to be outweighed by the risk of intestinal infarction. Patients who have good mesenteric blood flow demonstrated by angiography and who do not have peritoneal signs can be observed closely while other patients should proceed directly to laparotomy. Papaverine administration into the SMA during angiography has also been advocated because of concomitant arterial spasm that contributes to the ischemic process. A followup laparotomy has been recommended to confirm the viability of remaining small bowel. Prevention of recurrent venous thrombosis with warfarin is indicated for at least six months; however, a longer duration may be warranted if a thrombophilic state has been identified [73,74]. Low molecular weight heparin may also prove useful but long-term results are not yet available. (See "Treatment of lower extremity deep vein thrombosis".) Successful venous thrombolysis with streptokinase, urokinase, and tissue plasminogen activator has been reported in a small number of patients [8,64,75]. However, additional studies are necessary to demonstrate the safety and efficacy of venous thrombolysis compared to standard therapy. At this time, thrombolysis for SMV thrombosis should be considered experimental. Nonocclusive mesenteric ischemia Primary therapy for patients with nonocclusive mesenteric ischemia involves papaverine infusion through the angiographic catheter and an attempt to reverse the underlying condition leading to splanchnic

vasoconstriction. In patients without peritoneal signs, repeat angiography can be performed in 24 hours to verify resolution of vasoconstriction. Some authorities also advocate the concomitant use of intravenous heparin to prevent thrombosis in the cannulated vessel [2]. Surgical exploration should be limited to patients with peritoneal signs. Postoperative papaverine infusion is indicated. In patients who require segmental bowel resection, a delay in completing the intestinal anastomosis and aggressive reexploration may improve survival (mortality of 22 versus 42 percent in one series) [76]. Antiplatelet agents may be beneficial in the long-term management of these patients, although experience is limited [67]. We use standard dose aspirin. SUMMARY AND RECOMMENDATIONS

Acute insufficiency of mesenteric arterial blood flow accounts for 60 to 70 percent of cases of mesenteric ischemia and results in mortality rates exceeding 60 percent. Specific risk factors include advanced age, atherosclerosis, low cardiac output states, cardiac arrhythmias, severe cardiac valvular disease, recent myocardial infarction, and intra-abdominal malignancy. The diagnosis of AMI depends upon a high clinical suspicion, especially in patients with known risk factors (such as atrial fibrillation, congestive heart failure, peripheral vascular disease, or a history of hypercoagulability). Rapid diagnosis is essential to prevent the catastrophic events associated with intestinal infarction. However, early signs and symptoms of mesenteric ischemia are nonspecific, and definitive diagnosis often requires invasive testing, exposing the patients who typically have several comorbidities to risk. As a result, the diagnosis is often delayed. Mesenteric angiography remains the gold standard diagnostic study for acute arterial ischemia. Early and liberal implementation of angiography has been the major factor for the decline in the mortality of patients with acute mesenteric ischemia over the past 30 years. Thus, in patients for whom a high clinical suspicion of mesenteric ischemia is present, we suggest immediate angiography rather than other imaging modalities (Grade 2B). Such patients should also receive surgical consultation. Multidetector-row CT angiography appears to be an acceptable alternative in settings where obtaining early angiography is impractical, or there is only a moderate suspicion for acute intestinal ischemia, based upon the patient's clinical presentation. Accumulating evidence suggests that this imaging technique has a high degree of accuracy in diagnosing acute mesenteric ischemia, and it has the additional advantage of diagnosing alternative conditions.

The goal of treatment of patients with acute mesenteric ischemia is to restore intestinal blood flow as rapidly as possible after initial management that includes aggressive hemodynamic monitoring and support, correction of metabolic acidosis, initiation of broad spectrum antibiotics, and placement of a nasogastric tube for gastric decompression. Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES American Gastroenterological Association Medical Position Statement: guidelines on intestinal ischemia. Gastroenterology 2000; 118:951. McKinsey JF, Gewertz BL. Acute mesenteric ischemia. Surg Clin North Am 1997; 77:307. Reinus JF, Brandt LJ, Boley SJ. Ischemic diseases of the bowel. Gastroenterol Clin North Am 1990; 19:319. Ottinger LW. Mesenteric ischemia. N Engl J Med 1982; 307:535. Rosenblum JD, Boyle CM, Schwartz LB. The mesenteric circulation. Anatomy and physiology. Surg Clin North Am 1997; 77:289. Boley, SJ, Frieber, W, Winslow, PR, et al. Circulatory responses to acute reduction of superior mesenteric arterial flow. Physiologist 1969; 12:180. Zimmerman BJ, Granger DN. Reperfusion injury. Surg Clin North Am 1992; 72:65. Cappell MS. Intestinal (mesenteric) vasculopathy. I. Acute superior mesenteric arteriopathy and venopathy. Gastroenterol Clin North Am 1998; 27:783. Martinelli I, Mannucci PM, De Stefano V, et al. Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia: a study of 150 families. Blood 1998; 92:2353. Boley SJ, Brandt LJ, Sammartano RJ. History of mesenteric ischemia. The evolution of a diagnosis and management. Surg Clin North Am 1997; 77:275. Acosta S, Alhadad A, Svensson P, Ekberg O. Epidemiology, risk and prognostic factors in mesenteric venous thrombosis. Br J Surg 2008; 95:1245. Amitrano L, Brancaccio V, Guardascione MA, et al. High prevalence of thrombophilic genotypes in patients with acute mesenteric vein thrombosis. Am J Gastroenterol 2001; 96:146.

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