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Clinical approach to colonic ischemia

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ABSTRACTTypical clinical manifestations of colonic ischemia include rapid onset of mild abdominal pain and tenderness over the affected bowel, followed by a mild amount of hematochezia within a day of the onset of pain. Most patients have transient, nongangrenous ischemia, but some have severe ischemia.

KEY POINTS

  • The incidence of colonic ischemia is difficult to ascertain, as most cases are transient and either not reported or misdiagnosed.
  • Most cases are in the elderly.
  • The clinical presentation is not specific, as other conditions also present with abdominal pain and hematochezia.
  • The most common mechanisms are hypotension and hypovolemia caused by dehydration or bleeding that results in systemic hypoperfusion.
  • Endoscopy has become the diagnostic procedure of choice.
  • Although most patients can be treated conservatively with intravenous fluids, bowel rest, and antibiotics, some develop peritonitis or clinically deteriorate and require surgery.


 

References

Ischemic colitis is one of the diagnoses that should be considered when patients present with abdominal pain, diarrhea, and intestinal bleeding (others are infectious colitis, inflammatory bowel disease, diverticulitis, and colon cancer). Its incidence is difficult to determine, as many mild cases are transient and are either not reported or misdiagnosed. However, it is the most common type of intestinal ischemia1 and is responsible for an estimated 1 in 2,000 hospital admissions.2

In this review, we review the main causes of and risk factors for colonic ischemia and discuss how to diagnose and treat it.

BLOOD SUPPLY IS TENUOUS IN ‘WATERSHED’ AREAS

The superior and inferior mesenteric arteries have an extensive network of collateral blood vessels at both the base and border of the mesentery, called the arch of Riolan and the marginal artery of Drummond, respectively.

From Baixauli J, et al. Investigation and management of ischemic colitis. Cleve Clin J Med 2003; 70:920–934.

Figure 1. The arteries supplying the large intestine. In spite of an extensive network of collateral arteries, the watershed areas between major arteries are vulnerable to hypoperfusion.

During systemic hypotension, ischemic injury most often occurs at “watershed” areas, where the collateral arteries are small and narrow. These involve the terminal branches of the superior mesenteric artery supplying the splenic flexure and those of the inferior mesenteric artery supplying the rectosigmoid junction. (Figure 1).3,4 Although any area of the colon can be affected, approximately 75% of cases involve the left colon, and nearly 25% involve the splenic flexure.5

MANY POSSIBLE CAUSES AND FACTORS

Colonic ischemia is caused by a diminution of the colonic blood supply that is so severe that metabolic demands are not met. This diminution is most often the result of a decrease in systemic perfusion or an anatomic occlusion. Although it can be associated with many medical and surgical conditions (Table 1), a specific cause cannot be determined in most cases.

Age. Ischemic colitis most often occurs in elderly people; the average age is 70 years.6 Binns and Isaacson7 suggest that age-related tortuosity of the colonic arteries increases vascular resistance and contributes to colonic ischemia in elderly patients.

Hypotension and hypovolemia are the most common mechanisms of colonic ischemia. Hypotension can be due to sepsis or impaired left ventricular function, and hypovolemia can be caused by dehydration or bleeding. These result in systemic hypoperfusion, triggering a mesenteric vasoconstrictive reflex. Once the hypoperfusion resolves and blood flow to the ulcerated portions resumes, bleeding develops from reperfusion injury.8

Cardiac thromboembolism can also contribute to colonic ischemia. Hourmand-Ollivier et al9 found a cardiac source of embolism in almost one-third of patients who had ischemic colitis, suggesting the need for routine screening with electrocardiography, Holter monitoring, and transthoracic echocardiography.

Myocardial infarction. Cappell10 found, upon colonoscopic examination, that about 14% of patients who developed hematochezia after a myocardial infarction had ischemic colitis. These patients had more complications and a worse in-hospital prognosis than did patients who had ischemic colitis due to other causes.11

Major vascular surgical procedures can disrupt the colonic blood supply, and in two case series,12,13 up to 7% of patients who underwent endoscopy after open aortoiliac reconstructive surgery had evidence of ischemic colitis. In other series,14,15 the segment most often affected was the distal left colon, and the cause was iatrogenic ligation of the inferior mesenteric artery or intraoperative hypoperfusion in patients with chronic occlusion of this artery. Endovascular repair of aortoiliac aneurysm also carries a risk of ischemic colitis, though this risk is smaller (< 2%).16

Hypercoagulable states. The role of acquired or hereditary hypercoagulable states in colonic ischemia has not been extensively investigated and remains poorly understood.

Conditions that increase clotting can cause thrombotic occlusion of small vessels that supply the colon, leading to ischemia. In small retrospective studies and case reports,17–26 28% to 74% of patients who had ischemic colitis had abnormal results on tests for protein C deficiency, protein S deficiency, antithrombin III deficiency, antiphospholipid antibodies, the factor V Leiden mutation, and the prothrombin G20210A mutation. However, in what percentage of cases the abnormality actually caused the ischemic colitis remains unknown.

Arnott et al27 reported that 9 of 24 patients with ischemic colitis had abnormal results on testing for hypercoagulable conditions. Three patients had mildly persistent elevation in anticardiolipin antibodies, but none had the factor V Leiden mutation or a deficiency of protein C, protein S, or antithrombin.

Koutroubakis et al20 reported significantly higher prevalences of antiphospholipid antibodies and heterogeneity for the factor V Leiden mutation in 35 patients with a history of ischemic colitis than in 18 patients with diverticulitis and 52 healthy controls (19.4% vs 0 and 1.9%, 22.2% vs 0 and 3.8%, respectively). Overall, 26 (72%) of 36 patients had at least one abnormal hypercoagulable test result.

Most patients with ischemic colitis are relatively old (over 60 years), and many have multiple concomitant vascular risk factors, suggesting that many factors contribute to ischemic colitis and that thrombophilia is not necessarily the direct cause. Hypercoagulable states may play a more important role in young, healthy patients who present with chronic or recurrent colonic ischemia.

Because no large clinical trials have been done and data are scarce and limited to case reports and small retrospective studies, a hypercoagulable evaluation is reserved for younger patients and those with recurrent, unexplained ischemic colitis.

Even if we detect thrombophilia, nobody yet knows what the appropriate medical treatment should be. Although some cases of ischemic colitis with associated thrombophilia have been successfully treated with anticoagulants,28,29 the benefit of diagnosing and treating a hypercoagulable state in ischemic colitis is still unproven. Therefore, oral anticoagulation should be used only in those in whom a hypercoagulable state is the most likely cause of severe or recurrent colonic ischemia.

There are no official guidelines on the duration of anticoagulation in such patients, but we treat for 6 months and consider indefinite treatment if the ischemic colitis recurs.

Medications that should always be considered as possible culprits include:

  • Alosetron (Lotronex), which was temporarily withdrawn by the US Food and Drug Administration because of its association with ischemic colitis when prescribed to treat diarrhea-predominant irritable bowel syndrome.30 It was later reinstated, with some restrictions.
  • Digitalis
  • Diuretics
  • Estrogens
  • Danazol (Danocrine)
  • Nonsteroidal anti-inflammatory drugs
  • Tegaserod (Zelnorm)
  • Paclitaxel (Abraxane)
  • Carboplatin (Paraplatin)
  • Sumatriptan (Imitrex)
  • Simvastatin (Zocor)
  • Interferon-ribavirin31
  • Pseudoephedrine (eg, Sudafed).32

Endoscopic retrograde cholangiopancreatography can cause ischemic colitis if the rare life-threatening complication of mesenteric hematoma occurs.33

Chronic constipation can lead to colonic ischemia by increasing intraluminal pressure, which hinders blood flow and reduces the arteriovenous oxygen gradient in the colonic wall.34,35

Long-distance running can cause sustained bouts of ischemia, likely due to shunting of blood away from the splanchnic circulation, along with dehydration and electrolyte abnormalities. Affected runners present with lower abdominal pain and hematochezia. The colitis usually resolves without sequelae with rehydration and electrolyte correction.36

Vasospasm has been described as a cause of ischemia. During systemic hypoperfusion, vasoactive substances shunt blood from the gut to the brain through mesenteric vasoconstriction.37 This phenomenon can occur in dehydration-induced hypotension, heart failure, septic shock, or exposure to drugs such as antihypertensive medications, digoxin, or cocaine. Necrosis of the villous layer and transmural infarctions can occur with uninterrupted ischemia lasting more than 8 hours.38

Snake venom. The bite of Agkistrodon blomhoffii brevicaudus, a pit viper found in China and Korea, was recently reported to cause transient ischemic colitis due to disseminated intravascular coagulation. The condition resolved in about 10 days after treatment with polyvalent antivenom solution, transfusion of platelets and fresh frozen plasma, and empirically chosen antibiotics, ie, ampicillin-sulbactam (Unasyn) and metronidazole (Flagyl).39

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