Intestinal ischemia

Intestinal ischemia occurs if bowel perfusion cannot meet the metabolic demands of the intestine. This relative hypoperfusion may be the result of atherosclerosis, thromboembolic disease, or severe systemic hypotension. Intestinal ischemia is often classified based on its onset and location: acute mesenteric ischemia (AMI), chronic mesenteric ischemia (CMI), or colon ischemia (ischemic colitis). Each type has a different manifestation and treatment. AMI is a vascular emergency and manifests with sudden, severe abdominal pain; CMI manifests with chronic recurrent postprandial abdominal pain. Colon ischemia manifests with cramping abdominal pain and bloody diarrhea and is often self-limited, though, rarely, it may progress to fulminant bowel necrosis. Diagnosis is primarily made with cross-sectional imaging and CT angiography (CTA). Laboratory studies are used to determine disease severity and monitor the effects of resuscitation. Early diagnosis, surgical consultation, and definitive treatment with urgent surgical or endovascular revascularization are essential in AMI, which has a mortality rate of > 50%. Patients with CMI have a more favorable prognosis but still benefit from timely revascularization. Colon ischemia is primarily managed with supportive care and monitoring for symptom progression. Bowel perforation, intestinal infarct, and/or sepsis are associated with a poor prognosis, regardless of the type of intestinal ischemia.

Definition ^[1][2][3]

• Acute or chronic hypoperfusion of the colon; typically transient and self-limited (nongangrenous form), but can also result in severe acute ischemia with bowel infarction (gangrenous form)
• Often used interchangeably with the term ischemic colitis.

Epidemiology ^[2][4]

• Most common type of intestinal ischemia
• Most commonly affects individuals > 60 years of age
• ∼ 80% of cases are nongangrenous, resolving without surgery
• Isolated right-sided colon ischemia (IRCI): 10–25% of cases ^[5]

Etiology ^[3][6]

• Causes
  • Most commonly (∼ 95%) caused by transient hypoperfusion due to nonocclusive disease
  • Less commonly caused by occlusive disease (arterial thromboembolism or mesenteric venous thrombosis)
• Risk factors
  • Hypotension, hypovolemia: e.g., due to sepsis, dehydration, hemorrhage
  • Chronic disease: e.g., diabetes mellitus, cardiovascular disease, renal insufficiency
  • Thrombophilia: e.g., in antiphospholipid syndrome
  • Surgery: e.g., aortic aneurysm repair; , abdominal surgery affecting mesenteric arteries, cardiac surgery ^[7]
  • Medications and recreational drug use: e.g., vasoconstrictive drugs, immunomodulators, cocaine
  • Constipation, irritable bowel syndrome, colonic obstruction

Older patients with risk factors for atherosclerosis are at especially high risk for developing colon ischemia. ^[8]

Severe abdominal pain and bloody diarrhea after an abdominal aortic aneurysm repair is a classic manifestation of colon ischemia.

Pathophysiology ^[4][6]

• Intestinal blood flow of the superior mesenteric artery (SMA) and/or inferior mesenteric artery (IMA) is acutely compromised → intestinal hypoxia → intestinal wall damage → mucosal inflammation and possibly bleeding → possible progression to infarction and necrosis (gangrenous colon ischemia) → disruption of the mucosal barrier and perforation → release of bacteria, toxins, and vasoactive substances → life-threatening sepsis
• Tissue damage depends on the severity and duration of perfusion disruption.
  • Nongangrenous colon ischemia (mucosal or submucosal ischemia): 80–85% of cases; typically reversible
  • Gangrenous colon ischemia (transmural ischemia): 15–20% of cases; typically irreversible
• Tissue damage may be exacerbated by reperfusion injury. ^[9]
• Sites of compromise
  • Superior mesenteric artery
  • Inferior mesenteric artery
  • Middle and inferior rectal arteries
  • Watershed areas in the colon (i.e., the splenic flexure and the rectosigmoid junction) are at high risk for ischemia. ^[2][10]

Injury to the intestinal mucosa can occur after just 20 minutes of ischemia; transmural infarction and gangrene occur after 8–16 hours of ischemia. ^[6]

Clinical features ^[2][3]

• Classic presentation of colon ischemia
  • Sudden onset of cramping abdominal pain (usually in the left lower quadrant)
  • Urgent need to defecate
  • Bloody diarrhea or rectal bleeding within 24 hours of symptom onset
  • Symptoms resolve within 2–3 days.
• Signs of gangrenous colon ischemia
  • Progressive abdominal tenderness
  • Peritoneal signs
  • Fever
  • Ileus (absent bowel sounds)
• Signs of systemic complications
  • Acute abdomen with abdominal guarding and rebound tenderness
  • Systemic inflammatory response and/or signs of septic shock
  • Hypovolemic shock (e.g, due to dehydration or hemorrhage)

Consider colon ischemia in any patient with abdominal pain and/or bloody diarrhea without a clear infectious etiology, as many do not have the classic presentation of colon ischemia. ^[3]

In colon ischemia, pain is typically milder and more laterally located than in small intestinal ischemia. ^[3]

Red flags in colon ischemia

The following are poor prognostic markers:

• Clinical presentation
  • Male sex
  • Abdominal pain without rectal bleeding
  • Hypotension (SBP < 90 mm Hg)
  • Tachycardia (HR > 100 bpm)
• Diagnostics
  • WBC > 15,000/mm³
  • Hemoglobin < 12 mg/dL
  • LDH > 350 U/L
  • BUN > 20 mg/dL
  • Serum sodium < 136 mEq/L
  • Mucosal ulceration on colonoscopy

Classification

The severity of colon ischemia determines the appropriate approach to diagnostics and treatment. . ^[2]

• Mild colon ischemia: classic presentation of colon ischemia, no IRCI, and no colon ischemia red flags
• Moderate colon ischemia: 1–3 colon ischemia red flags
• Severe colon ischemia
  • > 3 colon ischemia red flags
  • OR any of the following:
    • Signs of peritonitis on examination
    • Pneumatosis intestinalis on imaging
    • Gangrene on colonoscopy
    • IRCI or pancolonic ischemia

Diagnostics ^[2][3][11]

Approach

• All patients with suspected colon ischemia
  • Obtain laboratory studies and stool studies.
  • Perform CT abdomen with IV and oral contrast.
  • Determine disease severity.
• Mild colon ischemia or moderate colon ischemia
  • Confirm the diagnosis with a colonoscopy and biopsy within 48 hours.
  • Consider CTA or MR angiography if suspicion for acute vascular occlusion remains.
• Severe colon ischemia, including IRCI
  • Routinely perform CTA, MR angiography, or mesenteric angiography to exclude persistent vascular occlusion.
  • Consider limited colonoscopy for diagnostic confirmation. ^[2][3]
  • Consider surgical exploration if the diagnosis remains in doubt.

CT abdomen is the preferred initial test for all patients with suspected colon ischemia.

Laboratory studies ^[3]

• There are no specific diagnostic laboratory studies for colon ischemia.
• Blood tests help assess the severity of colon ischemia; findings in severe colon ischemia include:
  • CBC: ↑ WBC and ↓ Hb
  • BMP: ↓ Serum Na⁺ and ↓ HCO₃^-
  • Other: ↑ Lactate, ↑ amylase, ↑ creatinine kinase, ↑ LDH
• Stool studies are indicated to rule out differential diagnoses (e.g., C. difficile-associated diarrhea).

Hallmark findings of severe colon ischemia include leukocytosis, metabolic acidosis, ↑ lactate, ↑ LDH, and ↑ CPK.

Imaging ^[8]

• CT abdomen with IV and PO contrast
  • Indication: required in all patients with suspected colon ischemia
  • Findings
    • Bowel wall thickening
    • Bowel edema
    • Pneumatosis intestinalis
    • Thumbprint sign: edematous thickening of the mucosa causing indentations in the large bowel wall
  • Additional benefit: may detect an alternative pathology
• Other imaging studies
  • CTA or MR angiography: indicated if there is suspicion of IRCI or AMI and in severe colon ischemia ^[2]
  • Splanchnic angiography: Consider if CT findings are negative but the patient has symptoms consistent with impending AMI. ^[2]
  • Plain abdominal radiograph
    • May be performed during urgent assessment of acute abdomen
    • Potential findings are nonspecific (e.g., air-filled, distended bowel).

Colonoscopy

Colonoscopy confirms the diagnosis, defines the distribution of the ischemia, and excludes other pathology.

• Indication: suspected mild colon ischemia or moderate colon ischemia
• Contraindications: signs of peritonitis or gangrenous bowel (e.g., pneumatosis on imaging)
• Findings
  • Edematous and fragile mucosa with erosions, ulcerations, and hemorrhagic lesions
  • Clearly defined segmental distribution of disease

Colonoscopy should be performed within 48 hours in patients with suspected colon ischemia. ^[2]

Differential diagnoses ^[3]

• Inflammatory bowel disease
• Infectious colitis
• Colorectal carcinoma
• Other differential diagnoses of acute abdomen

Treatment ^[2][3][12]

• Colon ischemia usually resolves spontaneously and requires no specific therapy.
• Surgical intervention is required in severe cases (e.g., patients with gangrenous bowel).

Initial management

• Initiate supportive care (e.g., analgesia, fluid therapy, and bowel rest) for all patients.
• Urgently consult surgery for patients with severe colon ischemia, signs of peritonitis, and/or hemodynamic instability.
• Consider antibiotic treatment for patients with moderate or severe colon ischemia.
• Disposition
  • Admit patients with severe colon ischemia to intensive care.
  • Consider outpatient management if symptoms are very mild.

Conservative management

• Supportive care
  • Complete bowel rest
  • IV fluid therapy
  • Analgesia
  • Consider parenteral nutrition if a prolonged disease course is anticipated.
• Antibiotic treatment
  • Consider in moderate colon ischemia and severe colon ischemia.
  • Give broad-spectrum antibiotics that cover both aerobic and anaerobic bacteria.
  • For potential regimens, see “Empiric antibiotic therapy for intraabdominal infections.”
• Management of the underlying condition, e.g.:
  • Treatment of hypercoagulable states ^[3]
  • Treatment of congestive heart failure
  • Treatment of constipation

Surgery

• Urgent indications
  • Signs of peritonitis
  • Massive bleeding
  • Portal venous gas or pneumatosis intestinalis
  • Toxic megacolon
• Other indications
  • Unsuccessful conservative management
  • Recurrent episodes of sepsis
  • Symptomatic stricture
  • Chronic segmental ischemia
• Procedures
  • Laparotomy and possible bowel resection
  • Creation of a temporary or permanent stoma
  • Revascularization procedures (rarely indicated in colon ischemia)

Complications

• Acute: bowel perforation, peritonitis, sepsis, multiple organ failure
• Chronic: chronic ischemic colitis, colon strictures

Prognosis ^[2]

• Overall mortality: 4–12%
• Recurrence rate: up to 10% within 5 years

Definition

• Acute reduction in arterial or venous blood flow to the small intestine; may result in bowel ischemia or infarct ^[13]

Epidemiology

• Most commonly occurs in individuals > 60 years of age ^[14]
• Prevalence in patients with acute abdomen: ∼ 1% ^[15]
• Mortality: 50–70% ^[13][16][17]

Etiology ^[13][15][16]

AMI has various etiologies, which manifest with similar clinical features despite having different underlying risk factors and pathology.

• Acute mesenteric artery embolism
  • Most common cause of AMI (causes 50% of all cases)
  • Risk factors include atrial fibrillation, myocardial infarction, valvular heart disease, and arterial interventions involving the aorta. ^[18]
  • Most commonly involves the SMA
• Acute mesenteric artery thrombosis
  • Causes ∼ 25% of cases
  • Risk factors include visceral atherosclerosis, arteritis, aortic aneurysm, and aortic dissection.
• Nonocclusive mesenteric ischemia
  • Causes ∼ 20% of cases
  • Most commonly occurs in critically ill patients with low cardiac output
  • Risk factors include hypotension and the use of vasopressors, digitalis, ergotamines, or cocaine.
• Mesenteric venous thrombosis
  • Least common cause of AMI (causes < 10% of all cases)
  • Risk factors include infection, malignancy, portal hypertension, estrogen therapy, and hypercoagulability disorders. ^[19]

Pathophysiology ^[15][16]

• Sudden interruption of blood flow to small bowel; → intestinal hypoxia → hemorrhagic infarction and necrosis → disruption of the mucosal barrier and perforation → release of bacteria, toxins, and vasoactive substances → life-threatening sepsis
• Sites of vessel occlusion
  • SMA (∼ 90% of cases)
  • Superior mesenteric vein (< 10% of cases)
  • IMA and celiac artery (uncommon)

Clinical features ^[13][15][16]

• Abdominal pain out of proportion to physical examination
• Diarrhea; bloody in later stages
• Nausea and vomiting, abdominal bloating
• Systemic signs of sepsis
• Peritonitis and acute abdomen in late stages
• Symptom onset and intensity may vary with the etiology of AMI. ^[13][15]
  • Acute mesenteric arterial embolism
    • Most acute onset and most severe pain of all AMI etiologies ^[15]
    • Patients may present with symptoms suggestive of an embolic source.
  • Acute mesenteric arterial thrombosis: subacute onset, less severe pain; occurs in patients with a history of abdominal angina ^[20]
  • Nonocclusive mesenteric ischemia: gradual onset of symptoms over several days; patients may be asymptomatic
  • Mesenteric venous thrombosis: mild, nonspecific symptoms that worsen gradually

Patients with acute mesenteric artery embolism typically present with the classic triad of severe abdominal pain, bloody diarrhea, and atrial fibrillation.

Patients with acute mesenteric artery thrombosis typically have known cardiovascular or peripheral vascular disease and/or symptoms of CMI in addition to acute symptoms.

Evaluate patients with atrial fibrillation and acute abdominal pain for acute mesenteric ischemia. ^[15]

Approach to management

• Perform an ABCDE survey and initiate resuscitation as indicated.
• Consult general surgery urgently for patients with peritonitis or hemodynamic instability.
• Consider differential diagnoses of acute abdomen.
• Obtain CTA to determine the site and possible etiology of the occlusion.
• Order routine laboratory studies, lactate, and emergency pre-op diagnostics (e.g., type and screen).
• Admit the patient to the ICU or organize direct transfer to the operating room.
• Consult vascular surgery and/or interventional radiology for definitive treatment.
• Start anticoagulation with full-dose heparin.
• Evaluate and treat the underlying disease (e.g., echocardiography for Afib).

Patients presenting with peritonitis and/or hemodynamic instability may need to proceed to surgery before imaging can be obtained.

Diagnostics ^{[13][15][21][22]}

CTA abdomen and pelvis ^[22]

• Indication: all patients with suspected AMI ^[22]
• Findings
  • Vascular pathology: embolism, thrombosis, stenosis, or dissection of mesenteric vessels
  • Bowel wall thickening, hypoperfusion, hemorrhage
  • Bowel dilation, air-fluid levels, mesenteric fat stranding
  • Pneumatosis intestinalis
    • A radiographic finding of gas within the wall of the intestine
    • Suggests transmural ischemia or infarction
  • Portal venous gas

CTA is the test of choice for AMI. ^[16][17]

Do not delay CTA while waiting for other diagnostic test results. ^[16][17]

Other imaging

• Consider catheter angiography in consultation with a specialist. ^[15][18][22]
• X-ray abdomen: may be considered only as a quick screening method for bowel perforation or obstruction ^[22]

Laboratory studies ^[13][15][16]

These can help establish AMI severity and guide resuscitation efforts but are not diagnostic for AMI. ^[13]

• CBC: leukocytosis, ↑ Hct (due to volume depletion) or ↓ Hct (due to GI bleed)
• ↑ Serum lactate
• CMP: electrolyte abnormalities, ↑ AST
• Blood gas: metabolic acidosis, ↓ HCO₃^-
• Other: ↑ D-dimer , ↑ amylase, ↑ CPK, ↑ LDH

Patients with AMI may have normal lactate levels and pH on initial presentation.

Treatment ^[13][16]

Initial treatment ^[17][23][24]

• Initiate supportive measures.
  • Administer supplemental oxygen.
  • Begin IV fluid resuscitation.
  • Provide additional hemodynamic support as needed.
  • Provide antiemetics and adequate pain management.
• Insert a nasogastric tube and keep the patient NPO.
• Start broad-spectrum IV antibiotics: See “Empiric antibiotic therapy for intraabdominal infections.”
• Begin parenteral anticoagulation with unfractionated heparin .
  • IV anticoagulation is indicated in all patients without contraindications to anticoagulation.
  • Coordinate heparin administration with the consulting surgical team.
• Consider early palliative care consultation in patients with extensive disease, particularly older patients.

Definitive treatment ^[15]

Definitive treatment is determined by the etiology of the AMI, the integrity of the bowel wall, and institutional resources .

• Surgical
  • Bowel resection (of necrotic segments)
  • Revascularization: open embolectomy and/or mesenteric bypass surgery
  • Damage control surgery (with or without temporary abdominal closure): for critically ill patients
  • Second-look surgery: to assess viability of remaining bowel
• Endovascular revascularization
  • Mechanical removal of the emboli or thrombus
  • Angioplasty with or without stenting of the mesenteric artery
  • Catheter-directed intraarterial infusion of thrombolytics or vasodilators (e.g., papaverine)

Emergency laparotomy is indicated if there are signs of peritonitis, intestinal infarct, or hemodynamic instability. ^[13][15]

Immediate anticoagulation and endovascular revascularization may be considered in hemodynamically stable patients with AMI and no signs of advanced bowel ischemia.

Patients who do not improve after endovascular intervention should undergo surgical intervention. ^[24]

Long-term management ^[13][23][24]

• Recommend lifestyle modifications for management of ASCVD.
• Optimize treatment of the underlying disease (e.g., Afib, HFrEF).
• Lifelong anticoagulation is typically recommended for patients with embolic AMI.
• Lifelong antiplatelet therapy is recommended after any revascularization procedure. ^[25][26]

Complications

• Peritonitis
• Sepsis
• Multiple organ failure
• Abdominal compartment syndrome

• Administer supplemental oxygen.
• Obtain IV access with two large-bore peripheral IVs.
  • Send laboratory studies.
  • Provide immediate hemodynamic support.
  • Start electrolyte repletion.
• Obtain CTA abdomen and pelvis.
• Admit to the ICU or organize transfer to the operating room.
• Urgently consult surgery and interventional radiology.
• Establish NPO status and insert an NG tube.
• Consider anticoagulation with IV heparin (after discussion with a surgeon).
• Start broad-spectrum IV antibiotics.
• Provide parenteral analgesia.
• Give antiemetics.
• Continue serial laboratory studies and physical examinations.

Definition ^[27]

• Mesenteric artery occlusive disease (MAOD)
  • Obstruction of blood flow in one or more of the major mesenteric arteries
  • May be symptomatic
• Chronic mesenteric ischemia (CMI):
  • Clinically symptomatic hypoperfusion of the bowel as a result of MAOD
  • Hypoperfusion is typically episodic but may be constant in advanced disease ^[27]

Epidemiology ^[27][28][29]

• MAOD is common, while CMI is rare.
• CMI most commonly occurs in adults > 60 years of age; ♀ > ♂

Etiology ^[27][28]

• Atherosclerosis (see “Risk factors for atherosclerosis”) is the main cause of CMI.
• Less common causes: median arcuate ligament syndrome, vasculitis, mesenteric venous thrombosis

Pathophysiology

• Slowly progressing stenosis of two or more of the main mesenteric arteries: SMA, IMA, and/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; these patients may be asymptomatic.
• Thrombus formation in addition to stenosis can lead to acute-on-chronic mesenteric ischemia, which leads to AMI.

CMI manifests as postprandial pain because oxygen demand increases significantly during digestion but the supply is limited by the fixed obstruction. ^[27][28]

Clinical features ^[28]

• Postprandial abdominal pain: begins 10–30 minutes after eating and lasts 1–2 hours
• Food aversion (sitophobia): fear of eating because of postprandial pain
• Unintended weight loss
• Nonspecific symptoms: e.g., nausea, diarrhea, bloating
• Abdominal bruit on auscultation

The recurrent dull postprandial pain associated with CMI is sometimes referred to as intestinal or abdominal angina.

Diagnostics ^{[15][18][27][28]}

Evidence of mesenteric artery stenosis is diagnostic for CMI in patients with suggestive clinical features and no other etiologies of postprandial abdominal pain. ^[27]

• Angiography: to confirm the diagnosis in symptomatic patients
  • Modalities
    • Duplex ultrasound of the mesenteric arteries: preferred screening test
    • CTA: preferred definitive diagnostic test
    • MR angiography: alternative if there are contraindications to CTA ^[18]
    • Catheter-based angiography: consider for therapeutic intervention or if noninvasive angiography is inconclusive
  • Findings: Mesenteric artery stenosis of > 70% is typically considered clinically relevant. ^[15][27][28]
• Laboratory studies: nonspecific; may show findings suggestive of malnutrition ^[15]
• Additional testing
  • Indicated in most patients to rule out malignancy and other causes of abdominal pain
  • May include upper and lower endoscopy, CT abdomen, MRI abdomen, and/or ultrasound abdomen

Differential diagnoses ^[28]

• Malignancy (e.g., gastric cancer, pancreatic cancer)
• Chronic cholecystitis
• Chronic pancreatitis
• Inflammatory bowel disease
• Irritable bowel syndrome
• Infectious gastroenteritis
• Celiac disease
• Peptic ulcer disease

Treatment ^{[15][18][27][28]}

Approach

• Offer revascularization to all patients. ^[27]
• Medically optimize patients prior to intervention (see “Preoperative management”).
• Provide nutritional therapy while awaiting revascularization.
• Monitor patients with MAOD for symptom development.

Revascularization

• Definitive therapy ^[27]
• Endovascular procedures (e.g., angioplasty, stenting) are preferred.
  • The SMA is the primary target for revascularization. ^[26]
  • Percutaneous mesenteric artery stenting is the most common procedure.
• Surgical revascularization is typically reserved for lesions not suitable for an endovascular approach.

Revascularization is recommended in all patients with CMI.

Nutritional therapy

• Frequent, small meals and a low-fat diet may provide some symptom relief.
• Total parenteral nutrition should only be considered as a temporary supportive measure.

Long-term management

• Management of ASCVD
• Long-term antiplatelet therapy after revascularization ^[26]
• Scheduled follow-up examinations for recurrent stenosis

Prognosis

• 5-year mortality for untreated CMI is close to 100%. ^[27][30]
• Symptoms are relieved in 95% of patients following revascularization. ^[23]