Mesenteric Ischemia

I. What every physician needs to know.

Mesenteric ischemia is a condition caused by impaired blood flow to the intestines with presentation ranging from mild chronic symptoms to a catastrophic acute episode caused by bowel necrosis and death.

Mesenteric ischemia can be classified by rapidity of symptom onset in to acute (AMI) versus chronic (CMI in short and also known as abdominal angina). AMI is characterized by sudden onset of hypoperfusion and is an emergency which without treatment is almost always fatal. CMI on the other hand is due to intermittent or constant vascular hypoperfusion.

Pathophysiology

As a response to ischemia, collateral mesenteric circulation opens to make up the oxygen demand however it is able to do so only for up to 12 hours. Intrinsic regulation of blood vessels occurs along with extrinsic regulation via neural and hormonal mechanisms. After a few hours, progressive vasoconstriction starts setting in reducing collateral flow. Vasoconstriction may persist despite reperfusion. Ischemic injury to tissue is sustained due to hypoxia as well as reperfusion.

II. Diagnostic Confirmation: Are you sure your patient has Mesenteric Ischemia?

The diagnosis of acute mesenteric ischemia requires a high index of suspicion because the clinical manifestations vary greatly depending on the severity and chronicity of the process. Many times this is a diagnosis of exclusion made after ruling out several possibilities. To appropriately manage mesenteric ischemia, physicians need to be aware of mesenteric vasculature anatomy, etiological mechanisms as well as the spectrum of presentations of this condition (detailed below).

Mesenteric vasculature

The gut is supplied by branches of the abdominal aorta in the following manner:

a. Celiac circulation – supplies the foregut (abdominal esophagus and superior half of the duodenum)

b. Superior Mesenteric circulation – midgut (lower half of the duodenum to the proximal two thirds of the transverse colon)

c. Inferior Mesenteric circulation – hindgut (splenic flexure to the upper part of the rectum)

d. Branches of bilateral hypogastric arteries (middle rectal artery) – cloacal derivatives (part of rectum)

Etiology

Arterial occlusion (embolism and thrombosis):

Arterial embolismis usually the commonest cause (30-50% of all cases) of mesenteric ischemia. Emboli may be of cardiac etiology (e.g., arrhythmias, valvular vegetations, vascular surgery) or from other sources in the presence of a right to left shunt. The superior mesenteric artery (SMA) is the commonest artery to be affected by emboli.

Arterialthombosisis another pathophysiological mechanism accounting for 25-30% of all mesenteric ischemic events. It is associated with the highest mortality. Arterial thrombosis may be caused by atherosclerosis plaque rupture or due to prolonged hypotension or even hypercoagulability due to any cause.

Venous occlusion (approximately 10% of all causes):

Venous thrombosis occurs less commonly with an associated mortality rate of 20-50%. Causes of venous thomboembolism include hypercoagulable states such as portal hypertension, malignancy, oral contraceptive use, clotting disorders, recent surgery, polycythemia, sickle cell disease. Smoking is a risk factor for venous thromboembolism in general.

Non-occlusive mesenteric ischemia (NOMI) causes (approximately 20%):

NOMI refers to mesenteric low flow states such as those caused by atherosclerosis, mesenteric vasospasm and hypotension due to any cause. Decreased vascular flow may also be seen in some rarer conditions such as vasculitis (as caused by Polyarteritis nodosa, Lupus Erythematosus, Dermatomyositis, Henoch-Schonlein purpura and Rheumatoid arthritis) and fibromuscular dysplasia.

NOMI predominantly affects the watershed areas (splenic flexure and rectosigmoid junction).

Extrinsic compression:

In rare causes, mesenteric vasculature may be compromised by tumors, strictures. In the condition known as ‘Median arcuate ligament syndrome’ also known as ‘Celiac compression syndrome’, the abdominal diaphragm may compress the celiac artery resulting in mesenteric ischemia. It is more commonly seen in females.

A. History Part I: Pattern Recognition:

When should you be concerned about Mesenteric Ischemia?

Various broad kinds of presentation patterns include:

Acute mesenteric ischemia (AMI):

A physician should suspect this in any patient with rapid onset of severe abdominal pain, which is often out of proportion to the physical exam findings (lacking involuntary guarding or peritoneal signs although these may occur later in the course). Nausea and vomiting may be a frequent accompanying factor.Bloody stool may occur in either acute or chronic ischemia.

Chronic mesenteric ischemia (CMI):

This condition should be suspected with any patient with long standing abdominal pain which is usually within the first hour of eating (post prandial) and in severe cases leads to sitophobia (fear of eating). Pain is of variable intensity and location. May be associated with nausea and vomiting. Patient may also report weight loss in addition to other complaints such as nausea and diarrhea.

Ischemic colitis:

Ischemic colitis is a form of mesenteric ischemia limited to the colon. It is caused by a low flow state, usually affects the elderly and is likely due to the shunting of blood away from the mucosa. It often develops insidiously and many a times, no specific cause can be found. It manifests with lower abdominal pain, rectal bleeding and in later cases patients may develop symptoms of peritonitis. The subacute variety is the commonest variant and manifests with a lesser degree of pain and bleeding.

B. History Part 2: Prevalence:

Mesenteric ischemia is an uncommon occurrence, accounting for less than 1 in 1000 hospital admissions. Arterial causes account for 55-80% of all cases (embolus and thrombosis as noted above) whereas venous causes occur much less frequently (about 10%) with the rest being due to non occlusive causes.

Acute mesenteric ischemia is associated with high mortality rates (59-93%) which is primarily due to a delay in diagnosis. The most recent American Gastroenterological Association position statement on this topic in 2000, noted that the mortality rate had not changed over last 70 years.

Chronic mesenteric ischemia is less common (less than 5% of all cases) and almost always due to atherosclerosis of the mesenteric vessels. Patients usually are elderly, smokers with diffuse atherosclerotic vascular disease. Females to male predominance is 3:1.

Ischemic colitis is predominantly a disease of the elderly with the majority of cases not progressing to gangrene.

C. History Part 3: Competing diagnoses that can mimic Mesenteric Ischemia.

Due to its non specific presentation findings, mesenteric ischemic will be in the differential of almost all causes of abdominal pain. It is often a diagnosis of exclusion and any elderly patient with unexplained abdominal pain should be evaluated for mesenteric ischemia.

Notably, ischemic colitis can mimic most forms of colitis (includes infectious, radiation colitis), diverticulitis and even colon cancer.

D. Physical Examination Findings.

Acute mesenteric ischemia is characterized by pain which is out of proportion to exam. This means that patient may not have involuntary guarding or rigidity (these may however be seen later in the course of the disease as bowel gangrene sets in). Some patients will have hypoactive bowel sounds and abdominal distension. Guiaic positive stool are also seen but may also manifest as frank hematochezia.

In patients with chronic mesenteric ischemia more often than not there are no physical exam findings. Sometimes there may be vague complaints of abdominal tenderness and blood in the stool. In some rare cases, an abdominal bruit may be heard over an area of turbulent flow due to vascular narrowing.

E. What diagnostic tests should be performed?

Early diagnosis is the key in managing mesenteric ischemia with the goal to prevent infarction. Notably, most diagnostic modalities do not show specific findings until it is too late.

Multi detector abdominal Computed Tomography (MDCT): This is the diagnostic test of choice since it allows for rapid and early detection of ischemia. Mural thickening is the commonest finding however other findings include pneumatosis intestinalis and portal vein gas.

Angiography:

This technique remains the gold standard for diagnosis of mesenteric ischemia however with development of the MDCT, it is now mostly used to confirm the diagnosis. It does require an interventional radiology specialist who may not always be available in all centers. ‘String of sausages’ sign (alternating dilatation and narrowing of intestinal branches) may be seen. Angiography offers the advantage of allowing option for immediate therapy with selective infusion of vasodilatory drugs.

Plain films of abdomen:

Findings are non specific and up to 25% patients may have a normal abdominal radiograph in early AMI. Some findings that may be seen include ‘thumbprinting’ and thickening of bowel loop (however are seen in less than 40% of patients on presentation). Air fluid levels and distension may also be seen.

Endoscopy:

This has been utilized to evaluate for mesenteric ischemia, however it can not appropriately evaluate much of the small bowel (hence lacking sensitivity). Colonoscopy may be used to look for colonic ischemia however it is done without any bowel preparation and with minimization of air insufflation (to minimize risk of perforation). Endoscopic techniques allow biopsies to be taken which can then be tested for ischemic damage.

Mesenteric ultrasound:

This has been used to detect hemodynamically significant stenoses (> 50%) in the abdominal vasculature however this has limited value in AMI.

Magnetic resonance testing:

Newer modality which can provide accurate images of the arterial and venous vasculature. However, technique is less reliable for detecting distal lesions and is less preferred than CT (which is quicker to do). Also limited by its cost, claustrophobia and surgical clips in the abdomen which will interfere with image interpretation.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

There are no laboratory tests which are diagnostic of mesenteric ischemia. However some commonly observed laboratory abnormalities include:

Leukocytosis:

In AMI, this is often profound and in excess of 20,000 (found in more than 90% patients). In CMI, mild leukocytosis may be the only abnormality found on blood work.

Lactate elevation:

This is the second commonest laboratory abnormality in AMI, indicating ongoing ischemia.

Metabolic acidosis:

Metabolic acidosis with anion gap is commonly seen in mesenteric ischemia especially in advanced cases.

D Dimer:

PositiveD Dimeris a non specific finding on blood work. Kougias et al., noted that in animal models, D dimer increased within 30 minutes from onset of intestinal ischemia and showed a time dependant increase.

Other abnormalities:

Other commonly observed laboratory abnormalities include elevations in serum amylase, LDH, CK. Elevations inserum phosphate and potassiumare usually late occurrences and indicate bowel necrosis.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

As noted above.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Barium enema has no role in the management of patients with acute mesenteric ischemia and introduction of barium may in fact potentially increase the risk for perforation. Barium will also interfere with interpretation of other more useful tests such CT.

III. Default Management.

Onceacute mesenteric ischemiais suspected, the cornerstone of treatment is fluid resuscitation and surgical consult while concurrently trying to identify the underlying cause. The goal of surgical management is to preserve as much of the bowel as possible. Follow up (second look) laparotomy after 24 hours is often done to ensure bowel viability.

Acute mesenteric venous thrombosis can be managed safely without surgery if there is no evidence of infarction. In these cases, immediate anticoagulation early in the course of the disease improves survival.

Most cases ofchronic mesenteric ischemiaare managed conservatively. In patients with chronic venous mesenteric vein thrombosis, long term anticoagulation may be recommended if found to have an underlying prothrombotic state.

Most cases of nonocclusive ischemic colitisresolve with conservative management in 1-2 weeks. Surgery is usually not required except for severe cases with colonic infarction or obstruction secondary to post-ischemic stricture.

A. Immediate management.

Acute mesenteric ischemia

Immediate management for AMI revolves around making an early diagnosis so as to completely avoid or at the very least, minimize infarction.

MDCT (or angiography) can localize embolus and should be ordered immediately. Surgical consult for an emergency laparotomy is recommended. Stat laboratory studies must include CBC, Basic Metabolic Panel and Lactate. Fluid resuscitation with aggressive monitoring is imperative at the outset to avoid hypotension (capillary leak will also lead to significant fluid shifts). Patient should have correction of metabolic acidosis and electrolyte abnormalities.

In advanced disease, other measures such as pressors (dobutamine, low dose dopamine or milrinone are preferred since they have less of an effect on the mesenteric perfusion) and placement of a nasogastric tube for abdominal decompression may also be needed. With onset of peritoneal signs, empirical broad spectrum antibiotics such as Imipenem may be used since bacterial translocation is a likely to occur with bowel wall damage.

Role of anticoagulation/lysis: Anticoagulation is indicated in mesenteric vein thrombosis. This is most commonly in the form of a Heparin drip used to avoid thrombus propagation.

Goal of surgery:Surgical evaluation should be requested immediately if considering AMI or any form of arterial insufficiency. Goal of surgical therapy is to prevent or minimize bowel gangrene. If there is evidence of peritoneal signs, surgical therapy would be indicated regardless of cause and normal laboratory values should not deter surgical exploration. Minimal bowel resection with a second look laparotomy is the foundation of surgical treatment.

Chronic mesenteric ischemia

Since CMI is usually not a life threatening condition, its management is initially conservative and an intervention may be considered for long term management. If CMI is due to a localized lesion(s), treatment options include surgical reconstruction and percutaneous transluminal angioplasty (PTA) with or without placement of a stent. In fact, endovascular therapy is predominantly limited to the chronic form of the disease. This will however, not be possible if disease is within the small vessels in which case the cornerstone of treatment will be to avoid hypotension by adequate fluid resuscitation.

Ischemic colitis

Management is based on severity of presentation. Most cases of nonocclusive ischemic colitis resolve in 1-2 weeks. Immediate management involves fluid resuscitation, antibiotics, analgesia. If signs of ileus are noted, a nasogastric tube should be placed. Surgical intervention is usually not required except for obstruction secondary to post-ischemic stricture.

B. Physical Examination Tips to Guide Management.

Acute mesenteric ischemia: Onset of peritoneal signs usually indicate bowel infarction and should prompt surgical evaluation if this has not already been done. Additionally, hypotension may occur indicating progressive deterioration and shock.

Chronic mesenteric ischemia: Since CMI presents less dramatically, the hospitalist should monitor abdominal pain. Improvement in pain frequency and intensity after intervention usually indicates an improving clinical picture.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Worsening anion gap metabolic acidodis, lactic acidemia, leukocytosis will usually indicate disease progress.

D. Long-term management.

For all patients, nutritional state should be corrected to improve outcome. In some cases, parenteral nutritional supplementation may be needed to avoid demands on the intestine. In all cases, management may involve long term antibiotics, anticoagulation, follow up care.

In acute mesenteric ischemia, long term management surrounds managing surgical outcomes and associated complications.

Patients with chronic mesenteric ischemia due to small vessel disease need to have medication strategies to avoid hypotension. As noted above, an intervention may be considered if an isolated lesion(s) can be definitively identified by mesenteric imaging.

In patients with ischemic colitis, there are usually no long term sequelae except in a minority (about 20%) of patients who develop persistent segmental colitis and strictures. These patients can present with recurrent abdominal pain, diarrhea and infections.

E. Common Pitfalls and Side-Effects of Management.

As noted above.

IV. Management with Co-Morbidities.

Patients with a history of vascular disease and diabetes are at higher risk for mesenteric ischemia. However there is no change in standard management.

A. Renal Insufficiency.

Based on severity of GFR compromise, some of these patients may not be candidates for contrast to diagnose the condition. Alternative imaging modalities such as ultrasound or magnetic resonance imaging will need to be considered. In severe cases, the diagnosis may need to be made intra-operatively.