Intestinal ischemia

Intestinal ischemia occurs when blood flow to the bowels is reduced. The condition can be acute or chronic and may affect the large and/or the small intestine. Possible causes for decreased blood flow include thromboembolism, atherosclerosis, and severe hypotension. Mild forms of intestinal ischemia lead to abdominal discomfort (e.g., postprandial pain) and a change in bowel habits (e.g., bloody diarrhea). In severe cases, infarction of intestinal tissue leads to perforation of the bowel, sepsis, and death. Early diagnosis and therapy are, therefore, essential and sometimes emergency surgery is vital. Imaging techniques (e.g., CT angiography, ultrasound, colonoscopy) are used to detect stenosis, occlusions, and/or mucosal changes. Chronic and mild acute forms are associated with better prognosis and patients benefit from revascularization procedures (e.g., stents, bypass surgery) and symptomatic therapy. Complications such as peritonitis and sepsis result in poor prognosis.

Intestinal ischemia is classified into three main types:

• Ischemic colitis (colonic ischemia): hypoperfusion of the large bowel, which is mostly transient and self-limiting (nongangrenous form), but can also lead to severe acute ischemia with bowel infarction (gangrenous form) ^[1]
• Acute mesenteric ischemia: acute inadequate blood flow to the small intestine (arterial or venous) that can result in bowel infarction
• Chronic mesenteric ischemia: constant or episodic hypoperfusion of the small intestine, usually due to atherosclerosis

Epidemiology

• Most common form of intestinal ischemia
• Mainly occurs in adults > 60 years ^[2]
• In ∼ 80–85% mild, nongangrenous form ^[3]

Etiology

Usually caused by transient hypoperfusion

• Thromboembolism
• Hypotension, hypovolemia (e.g., sepsis, dehydration, hemorrhage)
• Cardiovascular surgery (especially aortic repairs or cardiac bypass)
• Vasoconstrictive drugs
• Thrombophilias (e.g., antiphospholipid syndrome)
• Colonic obstruction from, e.g., tumors, adhesions

Pathophysiology

• Intestinal blood flow of the superior mesenteric artery (SMA) and/or inferior mesenteric artery (IMA) is suddenly compromised → intestinal hypoxia → intestinal wall damage → mucosal inflammation and possibly bleeding → may progress to infarction and necrosis (gangrenous type) → disruption of mucosal barrier and perforation → release of bacteria, toxins, vasoactive substances → life-threatening sepsis
• Depending on the degree of ischemia, there may be two types:
  • Nongangrenous (80–85%) ^[3]
  • Gangrenous (15–20%)
• Sites of compromise
  • Superior mesenteric artery (SMA): supplies the distal duodenum, jejunum, ileum, and the right colon from the cecum to the splenic flexure
  • Inferior mesenteric artery (IMA): supplies the left colon from the splenic flexure to the rectum
  • The splenic flexure and the rectosigmoid junction are at high risk for colonic ischemia because they are “watershed areas.”

The intestines can tolerate a state of ischemia for approx. 6 hours.

Clinical features

Typically presents with 3 clinical stages.

• Hyperactive phase
  • Sudden onset of crampy abdominal pain (usually left lower quadrant)
  • Bloody, loose stools
  • Most patients recover and do not progress beyond this phase
• Paralytic phase
  • Pain more diffuse
  • Bowel sounds become absent.
  • Bloating
  • Bloody stools cease
• Shock phase
  • Acute abdomen with abdominal guarding and rebound tenderness
  • Signs of septic shock

A classic case of ischemic colitis is a patient who presents with bloody diarrhea and severe abdominal pain after an abdominal aortic aneurysm repair.

Diagnostics

• Laboratory measures
  • No specific laboratory findings in mild ischemic colitis
  • In severe ischemic colitis:
    • ↑ Lactate, ↑ LDH, ↑ creatine kinase
    • Leukocytosis
    • Metabolic acidosis
• Imaging
  • Plain abdominal radiograph: insensitive, unspecific (air-filled, distended bowel), but helps exclude other disorders
  • CT scan: wall thickening, pneumatosis intestinalis (suggests transmural ischemia or infarction)
  • Thumbprint sign: an edematous thickening of the mucosa causes indentations in the large bowel wall
    • Appears like thumbprints in CT or plain radiograph
    • Unspecific sign for colitis (e.g., ischemic colitis, inflammatory bowel disease, infection).
• Colonoscopy
  • Procedure of choice in mild to moderate cases of ischemic colitis
  • Findings include edema, cyanosis, and/or ulceration of mucosa
• Exploratory laparotomy: in severe cases (possibly with resection)

Differential diagnoses

• See also “Acute abdomen.”

Therapy

• Mild to medium-severe forms
  • Supportive care (IV fluids, bowel rest, nasogastric tube in case of an ileus)
  • Antiplatelet drugs
  • Reduce risk of atherosclerosis (anticoagulation therapy)
• Severe forms (signs of peritonitis, sepsis): surgical intervention (laparotomy and bowel resection)

Complications

• Nongangrenous form: strictures or chronic ischemic colitis
• Gangrenous form: peritonitis → sepsis → multi-organ failure

Prognosis

• Ischemic colitis: mortality rate of approx. 6% ^[4]

Epidemiology

• Mainly occurs in adults > 60 years ^[5]
• Young people with atrial fibrillation, vasculitis (e.g., polyarteritis nodosa), or hypercoagulable states can also be affected
• Acute mesenteric ischemia: 0.1% of all hospital admissions ^[6]

Etiology

• Acute arterial embolism
  • Most common cause
  • Most commonly involves superior mesenteric artery (SMA)
  • Generally resulting from atrial fibrillation, myocardial infarction, valvular heart disease, or endocarditis
• Arterial thrombosis: due to preexisting visceral atherosclerosis, arteritis, aortic aneurysm, or dissection
• Nonocclusive mesenteric ischemia (NOMI)
  • Typically seen in critically ill people with low cardiac output
  • Potential causes include: hypotension, vasopressors, digitalis, ergotamines, cocaine
• Mesenteric venous thrombosis; (least common cause): Predisposing factors include infection, malignancies, estrogen therapy, and hypercoagulability disorders. ^[7]

Pathophysiology

• Sudden interruption of blood flow to small bowel; → intestinal hypoxia → hemorrhagic infarction and necrosis → disruption of mucosal barrier and perforation → release of bacteria, toxins, vasoactive substances → life-threatening sepsis
• Sites of interruption
  • SMA (∼ 90% of cases): supplies the distal duodenum, jejunum, ileum, and colon to the splenic flexure
  • Superior mesenteric vein (∼ 10% of cases): drains blood from the small intestine
  • Inferior mesenteric artery (IMA) and the celiac artery are less commonly affected.

Clinical features

• Periumbilical pain that is disproportionate to physical findings
• Nausea and vomiting
• Diarrhea: bloody in later stages (currant jelly stools)
• Gangrenous bowel: rectal bleeding and signs of sepsis (e.g., tachycardia, hypotension)
• Clinical courses
  • Acute arterial embolism: most abrupt and painful onset of all types
  • Acute arterial thrombosis: presentation less severe because patients have better collateral supply
  • Nonocclusive ischemia: symptoms develop over several days
  • Venous thrombosis: symptoms less dramatic, worsen gradually (e.g., abdominal discomfort evolves over a week)

A patient with acute arterial embolism typically presents with severe abdominal pain, fever, bloody diarrhea, leukocytosis, and atrial fibrillation.
A patient with acute arterial thrombosis typically has a known cardiovascular or peripheral vascular disease and/or symptoms of chronic mesenteric ischemia in addition to acute symptoms.

Diagnostics

• Laboratory findings
  • ↑ Lactate, ↑ LDH, ↑ creatine kinase
  • Leukocytosis
  • Metabolic acidosis
• Imaging
  • CT angiography: confirmatory test
    • Detects disrupted flow and vascular stenosis
    • Distended intestinal loops and air-fluid levels, wall thickening, pneumatosis intestinalis (suggests transmural ischemia or infarction)
  • MR angiography: an alternative to CT
    • Advantage: no radiation
    • Disadvantage: less accurate evaluation of the IMA
  • Ultrasound
    • Detection of distended intestinal loops and free fluid in the abdominal cavity in case of perforation
    • Color Doppler ultrasound to detect stenosis in arterial branches
• Other: for evaluation of the underlying disease (e.g., ECG for atrial fibrillation or myocardial infarction)

If acute mesenteric ischemia is suspected, quickly initiating imaging studies (CT angiography, color Doppler sonography) is essential. In cases with peritonitis or risk of shock, however, emergency surgery without prior imaging is indicated.

Differential diagnoses

• See “Acute abdomen.”

Treatment

• General and supportive measures: IV fluids, nasogastric tube; , analgesics, and broad-spectrum antibiotics
• Definitive management
  • Emergency laparotomy; : in the case of signs of advanced ischemia (e.g., peritonitis, sepsis) or hemodynamically unstable patient
    • Open surgical embolectomy or mesenteric artery bypass depending on the cause of occlusion
    • Resection of necrotic bowel segments
  • Immediate endovascular revascularization: in the case of hemodynamically stable patients without signs of advanced ischemia
    • Balloon angioplasty and stenting
    • Catheter-based pharmacologic (thrombolytics) and/or mechanical thrombectomy
  • Infusion of a vasodilator (e.g., papaverine) during arteriography to relieve occlusion and vasospasm
  • Heparin anticoagulation in cases of venous thrombosis
• Long-term measures
  • Reduce risk of further atherosclerosis (antiplatelet therapy and statin therapy)
  • Treat underlying cardiac disease (e.g., anticoagulation therapy in patients with Afib)

Acute management checklist for acute mesenteric ischemia ^{[8][9][10][11]}

• Urgent general/vascular surgery and interventional radiology consults
• NPO
• IV access with two large-bore peripheral IVs.
• Aggressive IV fluid resuscitation
• Avoid vasopressors, if feasible
• Electrolyte repletion
• Nasogastric tube insertion
• Administer supplemental oxygen.
• IV anticoagulation: unfractionated heparin infusion ^[9]
• Parenteral analgesics (see acute pain management) ^[12]
• Broad-spectrum IV antibiotics: See empiric antibiotic therapy for intra-abdominal infection.
• Parenteral antiemetics (such as ondansetron or promethazine )
• Serial abdominal examination
• Admit to surgical service/ICU or transfer to OR.

Complications

• Peritonitis
• Sepsis
• Multi-organ failure

Prognosis

• Acute mesenteric arterial ischemia: mortality rate of 60–80% ^[13]

Epidemiology

• A clinically manifested chronic mesenteric ischemia is rare
• Generally occurs in adults > 60 years ^[14]

Etiology

• See ”Risk factors for atherosclerosis” (e.g., high blood pressure, smoking, diabetes mellitus, high cholesterol levels).

Pathophysiology

• Slowly progressing stenosis of two or more main arteries (superior mesenteric artery (SMA), inferior mesenteric artery (IMA), or celiac artery) → postprandial mismatch between splanchnic blood flow and intestinal metabolic demand → postprandial pain
• If only one main artery is affected, collateral connections between the arteries can form and compensate for the reduced flow → patient may be asymptomatic
• Thrombus formation in addition to progressive stenosis can lead to acute-on-chronic mesenteric ischemia → acute mesenteric ischemia

Clinical features

• Some patients may be asymptomatic (see “Pathophysiology”)
• Abdominal/intestinal angina
  • Recurrent, dull, postprandial epigastric pain usually within the first hour after eating
  • Can lead to a fear of eating → weight loss and malabsorption
• Bloating, nausea, occasional diarrhea
• Abdominal bruit caused by stenosis of mesenteric vessels

A patient typically presents with postprandial abdominal pain (abdominal angina), food aversion, and weight loss.

Diagnostics

• No specific laboratory findings in chronic mesenteric ischemia
• Clinical suspicion → CT scan of the abdomen (identifies atherosclerotic vascular disease and rules out other abdominal disorders)
• CT angiography or MR angiography: High-grade stenoses of at least two major vessels must be established for diagnosis.
• Duplex sonography of the mesenteric vessels: best screening modality in an office setting

Differential diagnoses

• Malignancy
• Chronic cholecystitis
• Chronic pancreatitis
• Peptic ulcer disease

Therapy

• Nutritional support (frequent, small meals and low-fat diet) ^[15]
• Long-term anticoagulation therapy ^[16]
• Revascularization procedures to prevent bowel infarction in patients with abdominal pain and weight loss
  • Angioplasty and stenting
  • Mesenteric artery bypass surgery

Prognosis

• In chronic mesenteric ischemia, surgical revascularization and reduction of risk factors can lead to significant pain reduction.