Chronic Mesenteric Ischemia

Atherosclerosis is the most common cause of CMI, and patients frequently have a history of smoking, hypertension, and hyperlipidemia. They may also have evidence of atherosclerotic disease in other vascular beds, particularly coronary, cerebrovascular, renal, aortoiliac, and other peripheral arteries. Although it is much more uncommon, CMI may also be seen in association with vasculitis and other inflammatory conditions, such as lupus, Buerger’s disease, and radiation arteritis. Median arcuate ligament syndrome is a separate entity that may lead to symptoms of CMI and is caused by the compression of the celiac artery by the median arcuate ligament. Symptoms are classically exacerbated by full expiration.

Acute Mesenteric Ischemia

Nonocclusive Mesenteric Ischemia

Impaired intestinal perfusion in the absence of thromboembolic occlusion is termed nonocclusive mesenteric ischemia (NOMI) and makes up approximately 5% to 15% of cases.³¹ Visceral ischemia can occur from a low-flow state, which is exacerbated by the presence of any intestinal atherosclerotic disease. It is theorized that in such circumstances, in an effort to maintain cardiac and cerebral perfusion, excessive sympathetic output results in mesenteric vasospasm. NOMI most commonly occurs secondary to cardiac disease, particularly severe congestive heart failure, and in patients who have undergone cardiac surgery. Atrial fibrillation, commonly a cause of cardiac thrombi and visceral embolization, can also induce NOMI by reducing left ventricular function and causing low cardiac output. Other risk factors for NOMI include age, hypovolemia, systemic vasoconstrictors, vasoactive drugs (e.g., digoxin, α-adrenergic agents, β-receptor blocking agents, cocaine), aortic insufficiency, cardiopulmonary bypass, abdominal and cardiovascular surgery, abdominal compartment syndrome, and liver failure.^25,32

In recent years, NOMI has been increasingly observed in patients on hemodialysis. Quiroga et al³³ reported incidence rates more than 40 times greater among patients on hemodialysis compared with the general population. Using the Taiwan National Health Insurance Research Database, Li et al³⁴ similarly reported a 44-fold higher risk of mesenteric ischemia in patients on hemodialysis or peritoneal dialysis compared with the general population. Older age and a heavier burden of cardiovascular risk factors undoubtedly contribute to these disparities. In addition, patients with end-stage renal disease are frequently taking erythropoietin, which elevates red cell mass and can lead to relative hyperviscosity. However, hypotension during dialysis has been implicated as the most important and immediate precipitating risk factor for development of NOMI.³⁵ Therefore, special care should be made to avoid dialysis-related hypotension in patients at particularly high risk. High-risk patients include those who are older, are taking erythropoietin, have a longer history of dialysis, and are diabetics.^33,35

Mesenteric Venous Thrombosis

MVT constitutes 5% to 15% of all cases of mesenteric ischemia.^36,37 Involvement is usually limited to the superior mesenteric vein, but the inferior mesenteric, splenic, and portal veins can also be involved. MVT is classified as either primary (idiopathic) or secondary. Secondary MVT occurs when an underlying disease process is present; this type accounts for 90% of all patients with this disorder. Conditions associated with MVT can be categorized into three major categories: direct injury, local venous stasis or congestion, and thrombophilia. Causes of direct injury include abdominal surgery, trauma, and local inflammation, such as that seen with inflammatory bowel disease, pancreatitis, and diverticulitis.^38,39 Splanchnic venous stasis may occur in the case of increased intra-abdominal pressure, obesity, and intraoperative manipulation of the mesenteric vessels. Inherited or acquired hypercoagulable diseases, including protein C and protein S deficiency, myeloproliferative disorders, antithrombin III deficiency, antiphospholipid antibody syndrome, and factor V Leiden mutation, are frequent causes of thrombophilia and thus also predispose to MVT.⁴⁰

The extent of bowel ischemia depends largely on the degree of venous involvement and the presence of collateral vessels. The transition from normal to ischemic intestine is slower with MVT than with arterial occlusive disease.²⁵ Edema and hemorrhage of the intestinal wall are frequently seen, followed by focal sloughing of the mucosa.²⁵ The origin of thrombosis varies, depending on the etiologic process. When an intra-abdominal process is the cause, thrombosis begins in the larger mesenteric veins and progresses to involve the smaller venous arcades and arcuate channels.⁴¹ MVT caused by hypercoagulable conditions usually begins in the smaller mesenteric veins. Symptomatic acute MVT is associated with a 20% to 50% mortality rate.⁴¹ A Swedish population-based autopsy study showed that MVT-related death is more likely in patients with portal vein thrombosis, systemic venous thromboembolism, and obesity.⁴²

The most common symptom of AMI associated with arterial thromboembolic disease is the sudden onset of abdominal pain. Because of a lack of collateral flow to the visceral organs, the presentation of AMI is more dramatic and severe, often with rapid clinical deterioration. Nausea, vomiting, diarrhea, emptying symptoms, and distention can also occur. Classically, the pain is out of proportion to the findings on physical examination. Initially, bowel sounds are hyperactive as the failure to relax the bowel smooth muscle leads to emptying symptoms. Bowel sounds are typically diminished in the later stages. Abdominal guarding and rebound tenderness are absent in the early stages of AMI; however, as intestinal ischemia and infarction progress, these signs become more pronounced. They are typically late findings, so their absence should not delay the diagnosis and treatment of AMI. Other late findings include fever, oliguria, dehydration, confusion, tachycardia, and shock.²⁵ Metabolic abnormalities can include leukocytosis, metabolic acidosis, hyperamylasemia, elevated liver function values, and lactic acidemia.

Patients with NOMI or MVT typically present with a slower, more insidious clinical course. Frequently, patients with NOMI are critically ill, hospitalized, intubated patients who experience a sudden deterioration in their clinical condition. These patients are often administered intravenous pressors, worsening mesenteric vasoconstriction and thus decreasing splanchnic perfusion. In patients with MVT, fever, abdominal pain and distention, nausea and vomiting, and bloody stools are the most common findings. Dehydration and profound fluid shifts lead to bloody ascites and a hypovolemic state, causing further propagation of venous thrombosis.²⁵ Although nonspecific, normal D-dimer levels may help rule out MVT.⁴³

To develop better diagnostic criteria to reduce delays in diagnosis, Mitsuyoshi et al⁴⁴ reviewed their 13-year experience treating 22 patients with NOMI. Multidetector row computed tomography (MDCT) was unavailable at the time the first 13 patients were treated, and 9 subsequently died of intestinal necrosis. These first 13 cases were used to devise four criteria for determining which patients warranted MDCT evaluation once this technology became available: (1) ileus or abdominal pain, (2) catecholamine requirement, (3) episode of hypotension, and (4) gradual rise in serum transaminase level. If three of the four criteria were present, patients received MDCT and underwent treatment with high-dose intravenous prostaglandin E₁. Of the nine patients treated with this algorithm, only one died.

Chronic Mesenteric Ischemia

Postprandial abdominal pain and progressive weight loss are the most common symptoms in patients with CMI. Pain is often described as dull and crampy and located in the mid­epigastric region. Pain often occurs 15 to 45 minutes after a meal, and the severity varies according to the size and type of meal. Patients typically develop “food fear” and decrease their oral intake in anticipation of severe pain after meals. Consequently, weight loss is a common finding and in fact, when present, can help distinguish CMI from other functional bowel disorders when the diagnosis is in question.⁴⁵ Changes in bowel habits, nausea, and vomiting are less common findings. CMI is seen more frequently in elderly women, who represent 70% of patients. The variable nature of symptoms often makes the diagnosis confusing and can result in delayed treatment. The traditional risk factors for atherosclerosis are usually present. A heavy smoking history is frequently obtained, and the majority of patients also have a history of symptomatic manifestations in other vascular beds, most commonly cerebrovascular, coronary, and peripheral arteries.⁴⁶

Physical examination findings are usually nonspecific. Patients are commonly undernourished and cachectic (Fig. 151-2). An abdominal bruit can sometimes be auscultated but is not always present. Bowel sounds are frequently hyperactive. Guarding and rebound tenderness are usually absent. Low prealbumin and albumin levels are often seen owing to the patient’s chronic malnourished state.

DUS is a useful tool for the early, noninvasive diagnosis of visceral ischemic syndromes. Color Doppler scanning can be used to assess the flow velocities and resistance index in the splanchnic arteries and their arterial beds as well as to evaluate end-organ vascularity. The intestinal wall can also be assessed with a high degree of accuracy by high-resolution transabdominal ultrasound.⁴⁷ Transmural hemorrhage, inflammation, and necrotic thickening in the bowel wall can be imaged sonographically. Asymmetrical wall thickening with associated ileus as well as ascites and free peritoneal air can be seen in patients with AMI.⁴⁸ DUS combined with expiratory maneuvers is also an excellent screening examination for median arcuate ligament syndrome.

Moneta et al⁴⁹ performed blinded DUS studies in 100 patients who previously underwent arteriography of the celiac trunk and SMA. They hypothesized that lack of flow or a peak systolic velocity (PSV) in the SMA of greater than 275 cm/s, or no flow or a PSV of greater than 200 cm/s in the celiac trunk, was a reliable indicator of 70% or greater angiographic stenosis.⁵⁰ With use of these criteria, duplex sensitivity for detection of lesions in the SMA and celiac artery was 92% and 87%, respectively. Overall accuracy for detection of a 70% lesion in the SMA and celiac artery was 96% and 82%, respectively. The IMA is not generally assessed because it is generally difficult to visualize and is of lower clinical importance. However, patency of the IMA can usually be determined.

Limitations of transabdominal duplex scanning include the wide variation in examination quality, which is operator dependent. Patient-related factors, such as obesity, excessive intraluminal bowel gas, variation in local anatomy, and effects of respiration, can affect image quality.⁵¹ Care must be taken to clearly define the origin of each vessel to avoid inaccurate measurements. DUS is generally not recommended in the workup of AMI.

DUS is also the primary imaging modality used for surveillance after both bypass and stenting. However, no specific criteria exist for determining restenosis. Baker et al⁵² evaluated the accuracy and utility of DUS for detection of in-stent stenosis in 23 patients who underwent successful (<20% residual stenosis on completion angiography) mesenteric stenting for CMI (20 SMA alone, 3 both SMA and celiac artery). Preprocedure DUS was performed in 13 patients with a mean PSV of 464 cm/s. Initial surveillance DUS was performed in 21 patients at a mean of 0.9 month after revascularization. Mean PSV at this time was 335 cm/s, and for 12 of these patients, the first postoperative PSV in successfully stented vessels was higher than the 275 cm/s threshold used to diagnose high-grade native SMA stenosis. In addition, there was no correlation between surveillance PSV and the degree of angiographic stenosis seen at the time of re-intervention.

In their review of 107 patients who underwent endovascular therapy for CMI, Schoch et al⁵³ similarly reported that although 83% of patients had recurrent stenosis on surveillance DUS, 53% of patients remained asymptomatic and required no further intervention. These findings therefore mandate obtaining an early baseline DUS against which future surveillance scans can be compared. They also stress the importance of considering the clinical context and symptom recurrence in making the decision to re-intervene.

The predictive value of DUS for detection of disease recurrence after mesenteric bypass has also been studied. Liem et al⁵⁴ evaluated 167 duplex examinations used in the surveillance of 43 bypass grafts in 38 patients. On comparison of antegrade and retrograde bypass configurations, differences in mean PSV were demonstrated only at the inflow artery. There were no differences in PSV at the proximal or distal anastomosis, in the midgraft, or in the outflow artery. Between the first postoperative DUS examination and the latest follow-up scan (on average 38 months), PSV measurements did not change significantly. Graft failure occurred in two patients, both of whom had no findings to suggest impending occlusion on the DUS examinations immediately preceding failure. No predictors of graft thrombosis were identified on multivariable analysis.

Computed tomography (CT) is an accurate, noninvasive imaging modality for diagnosis of mesenteric ischemia. Modern MDCT enables imaging with excellent spatial and temporal resolution. A meta-analysis of six studies published between 1996 and 2009 on the diagnostic accuracy of MDCT in AMI showed a pooled sensitivity of 93% and specificity of 96%.⁵⁵ Advantages over conventional angiography include the relative ease and speed of performance; the rapid infusion of contrast agent through peripheral intravenous lines; and the ability to simultaneously image the mesenteric arteries, veins, and visceral organs. CTA is also useful for evaluating patency of previously placed grafts and stents. Common radiographic findings in the bowel wall related to AMI include increased thickening, dilatation, and attenuation, which can be easily detected with CT. Pneumatosis intestinalis, portal venous air, mesenteric edema, and ascites can also be detected. During the arterial phase of contrast infusion, the mesenteric vessels can be evaluated for thrombosis, embolus, dissection, and aneurysm. Venous engorgement and subtle intestinal findings may be identified in cases of mesenteric venous occlusion. A “target sign” may be seen in the superior mesenteric vein, with thrombus in the center of the lumen and surrounding contrast-enhanced blood flow peripherally. The portal venous phase is more accurate for diagnosis of MVT, and images during the venous phase may be acquired if the diagnosis is still in question or for surveillance of clot burden or extension in patients with MVT. In many centers, a biphasic scan, which includes a delayed venous phase in addition to an arterial phase, has been used in the diagnosis of AMI because it enables detection not only of arterial occlusion but also of MVT and improves the ability to detect changes in the bowel wall as well.

Disadvantages of CT include radiation, risk of contrast nephropathy, and hypersensitivity reactions to iodinated contrast agents. Inaccurate timing of contrast infusion during the arterial phase may provide indeterminate images and delay diagnosis. Because calcification at the vessel origins enhances in a similar fashion to intravenous contrast material, it is possible to underestimate the degree of stenosis. Therefore, the non–contrast-enhanced images should be reviewed. In addition, with careful adjustment of the window and level, calcification can usually be distinguished from intravascular contrast material. Last, CT serves strictly as a diagnostic modality; treatment must be performed through a separate angiographic procedure or laparotomy.

MRA is useful for diagnosis of mesenteric occlusive disease. Although MRA takes significantly longer to perform than CTA, it avoids the radiation exposure associated with CTA. Patients with hypersensitivity to iodinated contrast agents may also benefit from MRA. However, CTA has superior spatial resolution and allows better visualization of the IMA, peripheral splanchnic vessels, calcified plaque, and previously placed stents, giving it a distinct advantage.²⁶ For these same reasons, CTA is also preferred to MRA for surveillance after revascularization. Our standard workup includes DUS to screen those thought to have CMI. CTA is used routinely before intervention for AMI, CMI, and MVT.