Chronic mesenteric ischemia (CMI) usually results from long-standing atherosclerotic disease of 2 or more mesenteric vessels. Other nonatheromatous causes of CMI include the vasculitides, such as Takayasu arteritis. Symptoms are caused by the gradual reduction in blood flow to the intestine. (See Presentation.)
In 1958, Shaw and Maynard described the first thromboendarterectomy of the superior mesenteric artery (SMA) for the treatment of both acute mesenteric ischemia (AMI) and CMI. Several other surgical procedures have since been attempted, ranging from reimplantation of the visceral branch into the adjacent aorta to using an autogenous vein graft. In 1972, Stoney and Wylie introduced transaortic visceral thromboendarterectomy and aortovisceral bypass, which have proved to be highly effective techniques.
Since the introduction of endovascular treatment in 1980, there has been an increase in the use of this modality. (See Treatment.) A systematic literature review from 2013 showed that endovascular treatment was used in 50.48% of cases between 2001 and 2010, compared with 22.3% between 1986 and 2000.
For patient education resources, see the Digestive Disorders Center and Cholesterol Center, as well as Abdominal Pain in Adults and Coronary Heart Disease.
Mastery of the anatomy of the mesenteric vessels is essential to management of CMI, though the wide array of vascular variations can make such mastery difficult to achieve. The primary vessels supplying the mesentery are as follows:
The celiac trunk arises from the ventral surface of the aorta at the T12-L1 vertebral body. It courses anteroinferiorly before branching into the common hepatic, splenic, and left gastric arteries. Numerous variations have been observed, but further discussion of these is beyond the scope of this article.
The hepatic artery gives off the gastroduodenal artery, which branches further into the right gastroepiploic artery and the anterosuperior and posterosuperior pancreaticoduodenal arteries. The right gastroepiploic artery communicates with the left gastroepiploic artery, which is an immediate branch of the splenic artery. The anterosuperior and posterosuperior pancreaticoduodenal arteries communicate with the corresponding inferior branches from the SMA.
The splenic artery gives off the left gastroepiploic artery and the dorsal pancreatic artery, which supplies the body and tail of the pancreas and communicates with the anterosuperior pancreaticoduodenal and gastroduodenal arteries and, sometimes, the middle colic artery or SMA.
The left gastric artery communicates with the right gastric artery along the posterior aspect of the lesser curvature of the stomach.
The celiac trunk supplies most of the blood to the lower esophagus, stomach, duodenum, liver, pancreas, and spleen.
The SMA comes off of the ventral aorta and gives off the inferior pancreaticoduodenal artery and the ileocolic, middle colic, right colic, jejunal, and ileal branches.
The inferior pancreaticoduodenal artery gives rise to the corresponding anteroinferior and posteroinferior branches, which anastomose with their superior counterparts (see above). This communication is an important connection that helps maintain bowel perfusion in the setting of mesenteric ischemia.
The ileocolic artery supplies the ileum, cecum, and ascending colon, whereas the middle colic artery supplies the transverse colon and communicates with the IMA. The right colic artery typically branches at the same level as the middle colic artery. The right and middle colic arteries are important suppliers of blood to the marginal artery of Drummond and give rise to the terminal vasa recta, which provide blood to the colon.
The IMA is the smallest mesenteric vessel and comes off the anterior aorta. It provides blood to the distal transverse, descending, and sigmoid colon, as well as to the rectum.
Many communications with the SMA exist within the mesentery, and rectal branches offer communication of the visceral blood supply with the common blood supply.
The watershed area, near the splenic flexure, is thought to be more susceptible to ischemia secondary to poor arterial flow. Because this area is poorly developed, it has an increased propensity for ischemia.
Because of the multiple areas of potential collateral flow in the mesenteric system, at least 2 of the 3 main vessels must be occluded to produce CMI.
In more than 95% of patients, the process driving mesenteric ischemia is diffuse atherosclerotic disease, which decreases the flow of blood to the bowel. As the atherosclerotic disease progresses, symptoms worsen.
The interconnections between the celiac trunk, the SMA, and the IMA often permit easy compensation if stenotic lesions develop in 1 of these 3 vessels. Usually, therefore, at least 2 of the 3 major visceral vessels must be occluded or narrowed for CMI to develop. CMI with intestinal malperfusion is rarely seen in clinical practice, but when it does occur, it represents a serious and complex vascular disorder.
Although the pathophysiologic mechanism by which ischemia produces pain is still not completely understood, current physiologic understanding of splanchnic perfusion suggests a key role for the splanchnic circulation in the regulation of cardiovascular homeostasis.
In situations such as critical illness, major surgery, and exercise (all of which are characterized by increased demands on the circulation to maintain tissue oxygen delivery), gastrointestinal (GI) perfusion is often compromised earlier than other vascular beds are. Perhaps more important, this relative hypoperfusion often outlasts the period of the hypovolemic insult or low-flow state.[5, 6, 7]
Conditions less frequently involved in the pathogenesis of CMI are celiac artery compression syndrome (CACS; also known as median arcuate ligament syndrome [MALS]) and fibromuscular dysplasia (FMD). CACS entails external compression of the celiac trunk by the median arcuate ligament or the celiac ganglion.
Factors that predispose to atherosclerosis are associated with increased risk for CMI. These include the following:
When the arterial lumen is narrowed secondary to atherosclerosis, any increase in intestinal demand (as in eating) or decrease in intestinal supply (as in hypovolemia) can result in severe abdominal pain and possibly infarction. The risk factors for atherosclerosis are therefore pertinent to the development of CMI.
CMI is a rare diagnosis. In 1997, Moawad and Gewertz searched 20 years of literature and found only 330 cases. In 2013, Pecoraro et al included 1795 cases in their systematic review of 25 years of literature. Because many cases are not reported, the true prevalence could be much higher. Autopsy studies support this possibility, with findings of stenosis in as many as 30% of selected patients with a history of abdominal pain. No differences in frequency have been reported in various regions of the world.
CMI generally occurs in patients older than 60 years. Most studies have found it to be more prevalent in females than in males.
CMI, by itself, does not represent an important cause of mortality. When death does occur in patients with CMI, it could be related to mesenteric ischemia or to cardiac or other nonrelated causes (eg, cancer). Complications such as acute thrombosis or embolism are significant causes of increased mortality.
Patients with CMI often present with malnutrition secondary to their fear of postprandial abdominal pain. These patients may have a prolonged hospital course as a consequence of their chronically malnourished state.
Patients with chronic mesenteric ischemia (CMI) typically present with a history of the following:
The classic symptom is postprandial pain developing between 10 minutes and 3 hours after a meal. The pain can become so severe that the patient may develop a fear of eating and report recent weight loss.
Other nonspecific symptoms include the following:
Upon physical examination, the following may be found:
Workup for chronic mesenteric ischemia (CMI) may include the following:
Laboratory studies that may be considered include the following:
Arteriography is the criterion standard for the diagnosis of CMI (see the image below). Typically, the arteriogram shows occlusion of 2 visceral branches of the aorta, with severe stenosis of the remaining visceral branch, usually the celiac trunk or the superior mesenteric artery (SMA).
Angiogram of patient with chronic mesenteric ischemia. Note diffuse occlusive disease.
CTA has a sensitivity of 96% and a specificity of 94% for detecting CMI. According to the American College of Radiology appropriateness criteria, it should be a first-line alternative to conventional angiography. CTA plays an especially important role in diagnosing vascular disease of the celiac trunk and the SMA in CMI.
In a prospective analysis comparing CTA, MRA, and duplex ultrasonography, Schaefer et al found that CTA provided the best image quality, reached the highest level of agreement and significance in correlation in stenosis grading, and offered the best diagnostic accuracy.
MRA appears highly promising as a diagnostic tool. Until the use of fast contrast-enhanced techniques, it was limited by the acquisition time of phase-contrast or time-of-flight imaging and the development of motion artifacts. Advances in MRA technology have shortened acquisition times, so that it is now possible to obtain successive images in the arterial phase and then in the portal phase. MRA can be performed as an adjunct to any MRI examination.
MRA has been evaluated for the diagnosis of CMI and has been shown to provide accurate imaging of the mesenteric vasculature.[14, 15] However, its ability to obtain high-resolution images of the IMA is limited; because of the IMA’s anatomic course, only about 25% of the vessel can be depicted.
In general, MRA is not considered the initial imaging method of choice in an emergency setting.[16, 17]
Mesenteric duplex ultrasonography is a useful initial screening tool for CMI.[18, 19] It can visualize the SMA in approximately 90% of cases and the celiac trunk in approximately 80%. On the other hand, transabdominal ultrasonography is rarely able to visualize the inferior mesenteric artery (IMA), because of the vessel’s anatomic location and course. Peak systolic velocity has been widely used for diagnosing stenosis, with a cutoff value of 275 cm/s for the SMA and 200 cm/s for the celiac trunk.
Duplex ultrasonography is also used for assessing vascular patency after visceral bypass grafting or endovascular stenting. In a study by Baker et al, the peak systolic velocity in successfully stented SMAs remained higher than the peak systolic velocity threshold of 275 cm/s used for the diagnosis of high-grade native SMA stenosis. In addition, in-stent SMA peak systolic velocity did not significantly change over duplex surveillance for patients who did not undergo reintervention.
Thus, obtaining a baseline duplex ultrasonogram early after mesenteric stenting should be considered to compare future surveillance. An increase above this baseline or an in-stent SMA peak systolic velocity approaching 500 cm/s should be considered suggestive of in-stent stenosis.
It should be kept in mind that the clinical utility of duplex ultrasonography in this setting is largely dependent on operator training, bowel gas patterns, and patient body habitus. Intraperitoneal gas, respiratory movements, obesity, and previous abdominal surgical procedures may limit the sensitivity of this test.
For all practical purposes, ultrasonography should not be the initial diagnostic choice in the emergency department (ED).[16, 17]
Transected mesenteric vessels show diffuse atherosclerosis. The histologic findings from the bowel include atrophy of the tips of the villi, which leads to loss of the absorptive surface in the small bowel. The loss of the absorptive surface in conjunction with the patient’s fear of eating results in the malnourished state commonly seen in persons with CMI.
After the diagnosis of chronic mesenteric ischemia (CMI) is made or confirmed with arteriography, patients should undergo open or endovascular revascularization because of the risk of continued weight loss, acute infarction, perforation, sepsis, and death. Because of the high rate of thrombosis, medical management as the sole therapy is warranted only when the risks of revascularization outweigh the benefits. Nitrate therapy may provide short-term relief but is not curative. Anticoagulation therapy with warfarin is indicated.
Because of the high rate of coronary artery disease (CAD) in these patients, consultation with a cardiologist is warranted to evaluate the potential risks associated with surgery. All CMI patients should be evaluated for cardiopulmonary and renal disease before surgery is considered.
The prothrombin time (PT) and international normalized ratio (INR) should be monitored. Routine visceral duplex ultrasonography is recommended every 4-6 months. Obtaining a pretreatment base line is important.
In 2000, the American Gastroenterological Association released recommended algorithms for the diagnosis and management of mesenteric ischemia (see the image below). However, these recommendations were formulated before the availability of improved data from multidetector computed tomography (CT), as a result of which CT now plays a larger role in the diagnosis of mesenteric ischemia.
Management of chronic mesenteric ischemia. Solid lines indicate accepted management plan; dashed lines indicate alternative management plan. MRA=magne....
Indications for surgical management of CMI include the following :
Management options for CMI are as follows:
The choice between endovascular and open approaches to the treatment of CMI depends on multiple factors and should be tailored to the individual case. The 2 approaches have similar technical success and survival rates. Compared with open revascularization, stenting is associated with lower perioperative morbidity and mortality and shorter hospital stays. However, it is also associated with lower patency rates and higher recurrence rates, with increased need for repeat intervention.
Currently, it is common practice is to proceed with open revascularization if the patient has good life expectancy and fair nutritional status. Endovascular therapy is a good alternative in cases of poor nutritional status as a bridge to surgery or in cases with short life expectancy. Patient preference, age, comorbidities, and center expertise all play major roles in the decision.[3, 24, 25, 26, 27, 28]
The anatomy and the vessels affected also contribute to the treatment decision. In a study in which patients were treated with endovascular revascularization, clinical primary patency and primary patency were significantly higher for the superior mesenteric artery (SMA) group than for the celiac trunk group.
Several studies have found a high rate of success with percutaneous stent revascularization for CMI, though repeated interventions may be necessary.[30, 31, 32] A nonrandomized study showed that covered stents were associated with less restenosis, recurrences, and repeat interventions than bare metal stents in patients undergoing primary interventions or repeat interventions for CMI.
Surgical correction is accomplished by means of the following techniques:
Mesenteric artery reimplantation has been performed but, because of its technical difficulty, is not widely recommended.
Once a diagnostic arteriogram is obtained and surgery is deemed appropriate, intra-arterial papaverine is started to reduce the risk of arterial spasm. Any nutritional deficiencies (from the long period of malnutrition) or electrolyte imbalances should be corrected. In addition to arteriography, preoperative chest radiography and dipyridamole-thallium scanning may be considered. Bowel preparation is carried out the night before surgery, and the patient is on nil per os (NPO) status from midnight on.
After the procedure, because of the high rate of postoperative ileus, the patient is encouraged to ambulate as early as possible. Blood pressure is monitored to prevent hypotension, which can induce ischemia.
Because of the high prevalence of atherosclerosis, myocardial infarction (MI) is a common postoperative complication. The risk of MI can be reduced with the following steps:
Another common complication is acute renal failure in the immediate postoperative period. This can be prevented with the following steps:
Other possible complications include bleeding, infection, bowel infarction, prolonged ileus, and graft infection.
Kougias et al compared the effectiveness of balloon angioplasty or endovascular stenting (48 patients, 58 vessels) with that of open revascularization (96 patients, 157 vessels) in the treatment of CMI. The investigators found that members of the endovascular group had a shorter hospital stay than patients in the open revascularization group did (3 vs 12 days; P < .03) and that the 30-day mortality, frequency of in-hospital complications, and 3-year cumulative survival rate were the same for the 2 groups.
At 3 years after the procedures, however, the rate of cumulative freedom from recurrent symptoms was higher in the open-revascularization group than in the endovascular group (66% vs 27%; P < .02). The authors suggested that this was because the percentage of patients who underwent a 2-vessel procedure rather than a 1-vessel intervention was higher in the open group than in the endovascular group.
Another study compared the outcomes of patients with CMI who were treated with open mesenteric revascularization before (pre-endo) and after (post-endo) the preferential use of endovascular revascularization. The results showed that patients in the post-endo group presented with higher rates of hypertension, hyperlipidemia, cardiac interventions, and dysrhythmias; higher comorbidity scores; and more extensive mesenteric arterial disease.
However, the pre-endo and post-endo groups had similar outcomes for operative mortality, morbidity, length of stay, and immediate symptom improvement. At 5 years, primary patency rates, secondary patency rates, and recurrence-free survival rates were 82%, 86%, and 84% in the pre-endo group, respectively, and 81%, 82%, and 76% in the post-endo group, respectively.
Oderich et al studied 156 patients treated for mesenteric artery complications during angioplasty and stent replacement for CMI. The investigators concluded that complications occurred in 7% of patients, who experienced higher mortality, higher morbidity, and longer hospital stays.
Because CMI is a complication of diffuse atherosclerosis of the arterial tree, patients with this condition should maintain a low-fat diet, similar to that of patients with cardiac disease. Some patients report increased postprandial pain after eating large or fatty meals. Therefore, the diet should be appropriately altered to include small, multiple meals or low-fat meals.
As in patients with cardiac disease, regular exercise should be encouraged.
Drugs used in the management of chronic mesenteric ischemia (CMI) include heparin and warfarin for anticoagulation and intra-arterial papaverine for vasodilation.
Clinical Context: Warfarin is an anticoagulant that interferes with epoxide reductase, preventing production of vitamin K–dependent factors II, VII, IX, and X and proteins C and S. Because proteins C and S are the first factors to be inhibited, a prothrombic effect occurs during the initial few days after the start of warfarin therapy. Patients are started on heparin, then switched to warfarin when the prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR) are in the therapeutic range. Duration of action is 2-5 day.
Clinical Context: Heparin is a sulfated mucopolysaccharide. Its anticoagulant effect is related to its ability to activate plasma antithrombin. The main role of heparin in CMI patients is to prevent thrombus propagation.
Anticoagulants are given to prevent an acute thrombotic or embolic event.
Clinical Context: Papaverine is a benzylisoquinoline derivative with a direct nonspecific relaxant effect on vascular, cardiac, and other smooth muscle.
Clinical Context: Nitroprusside causes peripheral vasodilation by direct action on venous and arteriolar smooth muscle, thus reducing peripheral resistance. It is commonly given intravenously because of its rapid onset and short duration of action. It is easily titratable to reach the desired effect.
Used during arteriogram to decrease vasospasm in occluded arteries, with the objective of improving blood flow.
Clinical Context: Clindamycin is active against anaerobic gram-negative bacilli. It is a lincosamide that is useful in treating serious skin and soft tissue infections caused by most staphylococcal strains. It is also effective against aerobic and anaerobic streptococci, except enterococci. Clindamycin inhibits bacterial protein synthesis by inhibiting peptide chain initiation at the bacterial ribosome, which is where it preferentially binds to the 50S ribosomal subunit, causing bacterial growth inhibition.
Clinical Context: This drug combination inhibits the biosynthesis of cell wall mucopeptide and is effective during the stage of active growth. It consists of an antipseudomonal penicillin plus a beta-lactamase inhibitor and provides coverage against most gram positives, most gram negatives, and most anaerobes.
Clinical Context: Metronidazole is an imidazole ring-based antibiotic that is active against anaerobes. It is usually given in combination with other antimicrobial agents, except in the setting of Clostridium difficile enterocolitis, where monotherapy is appropriate.
Clinical Context: Aztreonam is a monobactam that inhibits cell-wall synthesis during bacterial growth. It is active against aerobic gram-negative bacilli.
Clinical Context: Cefoxitin is active against aerobic and anaerobic gram-negative bacilli. It is a second-generation cephalosporin that is indicated for management of infections caused by susceptible gram-positive cocci and gram-negative rods. Many infections caused by gram-negative bacteria, which are resistant to some cephalosporins and penicillins, respond to cefoxitin.
Clinical Context: Cefotetan is active against aerobic and anaerobic gram-negative bacilli. It is a second-generation cephalosporin that is indicated for management of infections caused by susceptible gram-positive cocci and gram-negative rods. Proper dosage and route of administration are determined on the basis of the patient's condition, the severity of the infection, and the susceptibility of the causative organism.
Clinical Context: Meropenem is a bactericidal broad-spectrum carbapenem antibiotic that inhibits cell-wall synthesis. It is effective against most gram-positive and gram-negative bacteria.
Antibiotic therapy must cover all likely pathogens in the context of the clinical setting.