Colonic Ischemia

Definition, Etiology, Pathogenesis

Colonic ischemia is caused by insufficient perfusion of the intestinal wall that leads to hypoxia, reperfusion injury, and colonic inflammation. Ischemic colitis is the most frequent form of gastrointestinal ischemia and a less severe form of colonic ischemia.

In most cases ischemic colitis is considered a disease of small blood vessels and results from a low-flow state with no single identifiable cause. It can also result from occlusion of arteries (atherosclerosis, embolism, or thrombosis) and/or rarely of mesenteric veins.

Arterial blood supply to the colon is derived from the superior mesenteric artery (SMA; ileocolic, right colic, and middle colic arteries) and inferior mesenteric artery (IMA; left colic artery, sigmoid arteries, and superior rectal artery at the end). The marginal artery of Drummond, which runs close to the colonic wall from the cecum to rectosigmoid junction, and the arc of Riolan, which—when present—connects the SMA or middle colic artery to the IMA or left colic artery near the mesenteric base, provide collateral blood flow to reduce the risk of colonic ischemia. Segments of the intestine that are particularly vulnerable to ischemia include the region of the splenic flexure (ie, Griffiths point, where the IMA and SMA circulations meet and rely on collateral blood flow) and rectosigmoid junction (ie, Sudeck point, where blood flow is dependent on the terminal branches of the IMA). The right colon is less frequently involved in ischemic colitis but is vulnerable to low-flow states and embolic occlusion of the SMA because the ileocolic artery is the terminal branch of the SMA. The rectum is relatively unaffected due to its robust blood supply from both the mesenteric and iliac arteries.

Clinical Features and Natural History

Colonic ischemia occurs more frequently in women and older patients.

1. Symptoms: The classic symptoms of ischemic colitis are mild to moderate crampy abdominal pain over the affected bowel (most often left sided), urgent need to defecate, and bloody diarrhea within 24 hours of onset. Physical examination is nonspecific.

2. Risk factors:

1) Medical conditions: Cardiovascular disease (eg, atherosclerosis, peripheral vascular disease, heart failure, atrial fibrillation, hypertension), diabetes mellitus, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis. Patients with acute medical conditions (eg, sepsis) are also at increased risk of developing ischemic colitis.

2) Procedures: Abdominal aortic aneurysm repair (due to ligation of the IMA), cardiopulmonary bypass, aortoiliac instrumentation.

3) Drugs: Constipation-inducing drugs (eg, opioids [increase intra-abdominal pressure and reduce blood flow]), immunomodulators (eg, anti–tumor necrosis factor alpha [increase thrombogenesis]), illicit drugs (eg, cocaine [may cause vasoconstriction, hypercoagulability, and endothelial injury]).

4) Rare risk factors include long-distance running, sickle cell crisis, and hypercoagulable states (usually found in younger patients presenting with ischemic colitis).

3. Natural history: Most cases are self-limited. Symptoms usually resolve within a few days and colonocyte healing occurs after a few weeks even when untreated. However, irreversible ischemia can occur in some cases. Necrosis and perforation of the colon wall with diffuse peritonitis and hemodynamic instability may develop rapidly. Long-term complications such as colonic strictures can occur. Mortality rates range from 4% to 12%. Increased mortality rates occur in patients with chronic kidney disease or COPD, in those requiring surgical management, and in patients with isolated right colonic ischemia or pancolitis.

Diagnosis

Diagnostic Studies

1. Laboratory tests:

1) Serology: There are no specific markers for ischemic colitis. Decreased hemoglobin (reflecting blood loss), decreased albumin levels (acute phase reaction), metabolic acidosis, and leukocytosis predict a more severe disease. In addition, investigations that may suggest advanced tissue damage include increased lactate, lactate dehydrogenase, creatine phosphokinase, and amylase.

2) Stool tests: Clostridioides difficile toxin assay, culture, and ova and parasite tests should be performed to exclude infectious colitis.

2. Imaging: Abdominal plain films are usually nonspecific and therefore not very helpful, apart from cases where they demonstrate signs of advanced ischemia (eg, thumbprinting indicating submucosal edema or free air indicating perforation). Nonspecific findings include ileus or colonic distension. Computed tomography (CT) with IV contrast has replaced barium enema and is the current standard of care. CT with IV contrast is timed for the portal venous phase and allows assessment of bowel perfusion as well as proximal arterial and venous circulation. Signs suggestive of ischemic colitis are nonspecific and include bowel wall thickening and fat stranding. Pneumatosis intestinalis (presence of gas in the bowel wall), portal venous gas, and absence of large bowel enhancement indicate severe disease often warranting surgical intervention. However, CT scans may be unremarkable in some cases. Computed tomography angiography (CTA; CT with IV contrast timed for a dedicated arterial, venous, and delayed phase with superior assessment of mesenteric arteries and veins compared with a CT with IV contrast timed for portal venous phase alone) or traditional angiography is only performed when acute mesenteric ischemia is suspected and in isolated right ischemic colitis to exclude large vessel disease.

3. Lower endoscopy: The diagnosis is confirmed with early colonoscopy or flexible sigmoidoscopy with biopsies within 48 hours. Careful insufflation and avoiding scope advancement much beyond the most distal extent of the disease (ie, advancing to the region of unhealthy colon and assessing it with minimal further insertion of the scope through unhealthy bowel) can reduce the risk of iatrogenic perforation. Contraindications to colonoscopy are peritonitis or signs of irreversible ischemic damage. Endoscopic findings include erythema, edema, hemorrhagic lesions, and/or ulcerations. Pathognomonic features are mucosal infarction and ghost cells. These lesions are frequently segmental with sharp transition between the normal and affected mucosa. The rectum is often unaffected due to its dual blood supply (as opposed to ulcerative colitis, which universally involves the rectum).

Treatment

1. Conservative management: Most cases (~80%) improve with bowel rest, fluid resuscitation, removal of precipitating factors, and nasogastric tube decompression if ileus is present.

2. Antibiotic therapy: Given the concern for bacterial translocation for ischemic colitis and the overall risk benefit ratio, broad-spectrum empiric antibiotics covering anaerobes and aerobic coliform bacteria are recommended for moderate to severe disease.Evidence 1 Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the evidence being based on animal studies and no human studies looking directly at the effect of antibiotics. Yoshiya K, Lapchak PH, Thai TH, et al. Depletion of gut commensal bacteria attenuates intestinal ischemia/reperfusion injury. Am J Physiol Gastrointest Liver Physiol. 2011 Dec;301(6):G1020-30. doi: 10.1152/ajpgi.00239.2011. Epub 2011 Sep 8. PMID: 21903760. Evidence is based mainly on experimental models and animal studies.

3. Anticoagulation: Anticoagulation is only indicated if the ischemic colitis is due to mesenteric venous thrombosis or cardiac embolization.

4. Surgical treatment: Surgery is required in up to 20% of patients. Indications for surgery include perforation; clinical, radiologic, or endoscopic features suggestive of gangrene (eg, peritonitis); failure of medical treatment; or rarely massive bleeding in the setting of ischemic colitis. Uncommonly, patients who remain symptomatic or have recurrent episodes weeks after presentation may require surgery. In patients who develop intestinal strictures, resection of the affected segments of the colon is indicated in the elective setting if the patients are symptomatic or if there is diagnostic uncertainty (ie, suspicion of cancer). Preoperative bowel preparation should be avoided due to the risk of causing further toxic bowel dilation or perforation. Laparoscopic or open technique can be used based on surgeon preference and patient stability. Resection of the affected segments of the intestines, with or without creating an end stoma and with or without a temporary abdominal wall closure for second-look laparotomy in 12 to 24 hours, is reserved for the most severe cases. Anatomic resection of bowel to limit reliance on collateral blood supply and the use of intraoperative adjuncts such as indocyanine green injection or Doppler probes for assessing the bowel's circulation viability may increase the success of operative intervention.