Continuing Education Activity

Bowel ischemia can classify as small intestine ischemia, which is commonly known as mesenteric ischemia and large intestine ischemia, which generally referred to as colonic ischemia. Intestinal ischemia occurs when at least a 75% reduction in intestinal blood flow for more than 12 hours. Abdominal pain is the most common symptom in patients with intestinal ischemia. This activity describes the etiology, evaluation, and management of bowel ischemia and highlights the role of the interprofessional team in improving care for patients with this condition.

Objectives:

• Identify the etiology and risk factors associated with bowel ischemia
• Outline the imaging options available to diagnose ischemic bowel.
• Summarize the treatment options of bowel ischemia.
• Describe interprofessional team strategies for improving care coordination and communication to treat bowel ischemia and improve outcomes.

Introduction

Bowel ischemia can affect a small or large intestine and can occur by any cause, which leads to intestinal blood flow reduction.[1] This is an uncommon medical condition, but it has a high mortality rate.[2] The intestine is mainly supplied by 2 major arteries, which include the superior mesenteric artery (SMA) and the inferior mesenteric artery (IMA). The SMA supplies the bowel from the lower part of the duodenum to two-third of the transverse colon. The IMA supplies a large intestine from the distal one-third of the transverse colon to the rectum. The celiac artery also has collaterals to supply the intestine.[3] Bowel ischemia can be classified as small intestine ischemia, which is commonly known as mesenteric ischemia[4] and large intestine ischemia, which generally referred to as colonic ischemia.[5] Two main areas in the colon, including splenic flexure (Griffiths point) and rectosigmoid junction (Sudek's point), are prone to ischemia. These are also known as the 'watershed' areas, which mean the regions in the colon between 2 major arteries that supplying colon. Splenic flexure is the area between SMA and IMA supplies, and the rectosigmoid junction is the region between the IMA and the superior rectal artery supplies.[6][7] These areas mostly supplied by the marginal artery; however, in 50% of the population, this artery is poorly developed. Watershed areas account for about 70% of ischemic colitis cases. The colon venous drainage is the parallel of arterial supply. The superior mesenteric vein drains the areas supplied by SMA, and an inferior mesenteric vein drains the left side of the colon and the rectum.[5] An acute decrease in mesenteric arterial blood flow accounts for 60% to 70% of patients with mesenteric ischemia. The rest of the causes are related to colonic ischemia and CMI.[8] Abdominal pain is the most common symptom in patients with intestinal ischemia. Some features of a patient can help to distinguish between the acute small bowel and colonic ischemia. Patient's characteristics, such as age over 60 years, not appearing severe ill, mild abdominal pain, tenderness, rectal bleeding, or bloody diarrhea, are the features that are more common in acute colonic ischemia.[9] Generally, an abdominal computed tomography (CT) scan is used in hemodynamically stable patients who present with acute abdominal pain.[10][11] In patients with high suspicious for intestinal ischemia, CT angiography and MR angiography are the initial tests.[12] Based on acute mesenteric ischemia (AMI) subtypes, different medication treatments have been suggested. Papaverine, through the angiographic catheter with the mechanism of relaxation of vessels vasospasm, can be used for all arterial forms of AMI and nonocclusive mesenteric ischemia.[13][14][15]

Etiology

Intestinal ischemia occurs when at least a 75% reduction in intestinal blood flow for more than 12 hours.[16] Bowel ischemia can be classified as small intestine ischemia, which is commonly known as mesenteric ischemia and large intestine ischemia, which generally referred to as colonic ischemia.[5][4]

Mesenteric Ischemia

Generally, mesenteric ischemia (MI) can be divided based on the timing of onset into acute and chronic.[1] Collateral circulation of the gastrointestinal tract can compensate for a 75% acute reduction in mesenteric perfusion for up to 12 hours without significant injury.[16] Etiologies of acute intestinal ischemia can categorize as mesenteric arterial embolism (50%), intestinal hypoperfusion or nonocclusive mesenteric ischemia (NOMI) (20% to 30%), mesenteric arterial thrombosis (15% to 25%) and mesenteric venous thrombosis (MVT)(5%).[17][18]

1-Mesenteric arterial embolism-Usually, mesenteric arterial embolism is seen in patients with cardiovascular disease. The common cardiac causes are including myocardial infarction, mitral stenosis, cardiac arrhythmias, ventricular aneurysm, and valvular endocarditis. Vascular causes can happen anywhere from the heart to the origin of SMA, which include mycotic aneurysm, atheromatous plaques in the aorta, or vascular aortic prosthetic grafts.[14]

2-Intestinal hypoperfusion or nonocclusive mesenteric ischemia (NOMI) usually involved who presents with a systemic shock, which can be due to cardiac, infection, or hypovolemia.[19] Nonocclusive causes an account for almost 95% of patients with colonic ischemia.[20]

3-Mesenteric arterial thrombosis-The risk of mesenteric arterial thrombosis is increased in patients with advanced age, peripheral artery disease, traumatic injury, and low cardiac output states.[8][21]

4-Mesenteric venous thrombosis can happen in patients with acquired and inherited hyper coagulopathy conditions.[22]

Chronic Mesenteric Ischemia

In chronic mesenteric ischemia, the diffuse atherosclerotic disease is an account for 95% of cases. Female with age greater than 60,[23], history of smoking[24], cerebrovascular disease, coronary heart disease, or peripheral artery disease in the lower extremity can increase the risk of chronic intestinal ischemia.[25] The rest of the 5% include vasculitis, fibromuscular dysplasia, Takayasu arteritis, malignancy, and radiation.[26]

Epidemiology

An acute decrease in mesenteric arterial blood flow causes 60% to 70% of patients with mesenteric ischemia. The rest of the causes are related to colonic ischemia and chronic mesenteric ischemia.[8] Mesenteric ischemia (MI) accounts for 0.1% of all hospital admissions, despite this being a rare medical condition. It has high mortality rates ranging from 24% to 94%.[2] The incidence of colonic ischemia is approximately 16 cases per 100,000 person-years, and it is increasing over time.[27] Ischemic colitis is reported for 1 in 2000 hospital admissions.[28] This medical condition is more common in females.[29]

Pathophysiology

The splanchnic circulation varies based on the feeding or fasting state. Despite high intestinal vasculature, oxygen extraction is low from the intestinal arteries. This physiology permits the liver to receive enough oxygen through the portal vein.[30] In the postprandial state, intrinsic autoregulation of blood flow helps the delivery of blood flow from the intestine to the brain.[7] Intestinal ischemia happens when inadequate oxygen delivered to the intestine. However, intestinal injury occurs by low perfusion and reperfusion of intestinal tissues. Low perfusion can cause intestinal injury when mesenteric perfusion pressure decreases about 30 mmHg or reduction of 45 mmHg in mean mesenteric arterial pressure. Physiologically, the intestine can compensate for about 75% of the reduction in mesentery blood flow for 12 hours without significant injury due to vasodilation of collateral circulation and increased oxygen extraction. However, after a prolongation of low perfusion or hypoxemia, progressive vasoconstriction leads to reducing collateral flow and subsequently full-thickness necrosis of the intestinal wall and perforation.[8][17] Reperfusion injury after ischemia can be observed due to the release of toxic byproducts of ischemic injury, free oxygen radicals, and neutrophil activation.[31]

Histopathology

Necrosis of the mucosal villi is the initial change, which usually happens within 3 to 4 hours after intestinal ischemia. Following that, transmural, mural, or mucosa infarction can happen. Splenic flexure and rectosigmoid junction are the common susceptible area to hypoperfusion and hypoxia. Initially, in response to the injury, the intestinal wall becomes congested. It then appears edematous, friable, and hemorrhagic. Without intervention, bowel hemorrhage can occur within 1 to 4 days. Subsequently, enteric bacteria leads to intestinal gangrene and perforation.[32][33]

History and Physical

A careful review of the patient's medical conditions and family history is essential for the evaluation of intestinal ischemia. The history of cardiac disease [34], aortic surgery, peripheral artery disease, hemodialysis, vasoconstrictive medications, acquired or hereditary thrombotic conditions, hypovolemia, and inflammation or infections should increase suspicion of intestinal ischemia in a patient with abdominal pain.[35] Abdominal pain is the most common symptom in patients with intestinal ischemia. Some features of a patient can help to distinguish between the acute small bowel and colonic ischemia. Patient's characteristics, such as age over 60 years, not appearing severe ill, mild abdominal pain, tenderness, rectal bleeding, or bloody diarrhea, are the features that are more common in acute colonic ischemia.[9] The features of the pain, physical exam, and accompanying symptoms can help to distinguish the etiology of intestinal ischemia. In mesenteric artery embolism, usually, the pain is sudden onset, severe, periumbilical, and often accompanied by nausea and vomiting.[36] The pain in thrombotic mesentery ischemia commonly presented postprandial.[37] In mesenteric veins thrombosis, the pain usually described as wax and wane before the definite diagnosis.[38] The patients with nonocclusive mesenteric ischemia do not have classic severe pain and typically present in patients with a history of hypotension, hypovolemia, cardiac arrhythmia, and heart failure.[39] Patients with chronic mesenteric ischemia usually present with recurrent abdominal pain after eating and subsequently can cause patients losing weight.[26] Patients with acute colonic ischemia commonly are presented with sudden onset cramping abdominal pain, which usually involves the left side. The pain can be accompanied by an urgent desire for a bowel movement. Instead of periumbilical pain in small intestine ischemia, patients with colonic ischemia usually feel the pain laterally.[40][41] Physical examination in patients with intestinal ischemia can vary from normal to peritoneal sign (rebound tenderness and guarding) based on the time course of the onset.[42]

Evaluation

Laboratory tests in intestinal ischemia are nonspecific. In the early stage of the disease, complete blood cell count can be normal, but with the progression of the ischemia, leukocytosis with the leftward shift, elevated amylase, and lactate dehydrogenase levels may be observed.[43] Based on underlying risk factors, laboratory studies can be abnormal. In MVT, patients need to evaluate for hypercoagulopathy states such as examined for protein C and S and antithrombin III deficiency, lupus anticoagulant, and platelet aggregation.[15][44] In CMI, abnormal laboratory tests, including leukopenia, hypoalbuminemia, and electrolyte abnormalities, may be observed secondary to malnourishment.[45] The diagnostic approach in patients with intestinal ischemia depends on the severity of symptoms. In patients with peritonitis signs, the diagnosis will be made by abdominal exploration. Plain radiographs, computed tomography angiography (CTA) or magnetic resonance angiography (MRA), invasive angiography, and duplex ultrasound are common radiology studies in patients with suspicion of intestinal ischemia.[42] Plain abdominal radiography is nonspecific; however, the presence of ileus with bowel loops distention, bowel wall thickening, and pneumatosis intestinalis can be suggestive for mesenteric ischemia. Plain abdominal radiography commonly used in patients with signs of sepsis and unstable hemodynamics.[46] Generally, abdominal CT is used in hemodynamically stable patients who present with acute abdominal pain. In addition to, rule out other causes of abdominal pain, some findings including pneumatosis intestinalis, portal vein gas, mesenteric edema, streaking of the mesentery, focal edematous bowel wall, abdominal gas pattern, and solid organ infarction can be suggestive for acute mesenteric ischemia in abdominal CT scan.[10][11] In patients with high suspicious for intestinal ischemia, CT angiography, and MR angiography are the initial tests. However, the CTA is preferred over MRA due to lower cost, white availability, and speed.[12]The CT scans should be done without oral contrast due to oral contrast that can obscure the bowel wall enhancement and the mesenteric vessels, which both lead to a delay of definitive diagnosis.[47][48][49][50] Angiography usually reserved in patients with high suspicious of AMI with negative CTA or patients with NOMI. Diffuse stenosis in mesenteric vessels with the absence of occlusive lesions is the finding in NOMI patients by angiography.[51] The role of duplex ultrasound is just limited to the detection of clots in the proximal of the main vessels. In addition to that, peritoneal gas, previous abdominal surgical intervention, obesity can decrease the sensitivity of duplex ultrasound.[42] In hemodynamically stable patients with clinical features of acute colonic ischemia, including abdominal pain, urgent desire to defecation, diarrhea, and lower gastrointestinal bleeding in addition to common imaging studies (plain radiography, CTA) may require sigmoidoscopy or colonoscopy and biopsy for definitive diagnosis.[52] If colonic ischemia is suspected, colonoscopy preferred to be performed within 48 hours of initial symptoms rather than later.[53][54]

Treatment / Management

Acute Mesenteric Ischemia

Due to high mortality rates in patients with AMI, it is essential for urgent medical treatment. Initial treatments include maintenance of adequate oxygen saturation, hemodynamic stability, and correction of electrolyte abnormalities. Typically, 2 to 4 units of blood products should be made available. Vasopressors should be avoided. Broad-spectrum antibiotic therapy with coverage of colonic flora is the recommended intervention to prevent and treat sepsis. Bladder catheterization, nasogastric tube decompression, correction of acid/base abnormalities, and intravenous fluid administration are implemented preoperatively. The patient's pain should be controlled, preferably by using parenteral opioids.[13][55][15] Based on intestinal ischemia subtypes, suggestions have included different treatment options.

Endovascular Intervention Versus Surgical

The data indicate that in patients with acute mesenteric arterial occlusion, an endovascular intervention can be as effective as traditional surgical.[56][57][58]

Endovascular Intervention

• Pharmacologic or Mechanical Thrombectomy

(1) Mechanical thrombectomy

Access to SMA can is possible through the femoral or brachial artery (antegrade approach). Despite the antegrade approach, in a retrograde approach, the device exposed SMA distal to the obstruction at the time of laparotomy.[59][60] After gaining access to SMA, the stiff wire goes into the ileocolic branch of the SMA and directly aspirate the thrombus with a 20 mL syringe over the catheter.[61]

(2) Catheter-directed thrombolysis

Catheter-directed thrombolysis is indicated in patients with distal mesenteric embolization or incomplete aspiration embolectomy.[62] Papaverine, through the angiographic catheter with the mechanism of relaxation of vessels vasospasm, can be used for all arterial forms of AMI and NOMI.[13][14][15] However, papaverine infusion should not be used simultaneously with heparin due to an increased risk of papaverine precipitation.[63] In patients with embolic AMI, the pharmacomechanical thrombolysis is recommended within the 8 hours of symptoms initiation in selected patients. The absolute contraindications for thrombolysis are in patients with bowel necrosis or signs of peritonitis. Recent studies suggested reteplase or tenecteplase infusion are more favorable compared to alteplase due to lower risk of non-intracranial bleeding.[64][65][66] The initiation of heparin can prevent additional clot formation, and conversion to oral warfarin and continued for at least six months is always indicated.[67][68]

• Balloon Angioplasty

Mesenteric artery angioplasty is usually followed by stenting, which may be appropriate in select patients. Based on device insertion, it can be classified in 2 fashions.[59][60] In an anterograde fashion, the device inserts through the aorta into the SMA, which is usually performed in chronic ischemia. While in an open retrograde fashion, the device introduces through the SMA distal to the obstruction. It is favorable in the setting of an unsuccessful thrombectomy or when the surgical bypass is not available.[56][69][70]

 2-Surgical

• Abdominal Exploration and Damage Control

Regardless of the etiology of intestinal ischemia, in patients suspected of intestinal infarction or perforation based on clinical, radiographic, or laboratory tests, exploratory laparotomy should not be delayed.[15][19] In NOMI or colonic ischemia, approximately 20% of patients have required surgery.[71] Resection of the infarcted intestine is strongly indicated. For diagnoses of the low perfused bowel regions, intraoperative Doppler US and fluorescein IV infusion with an examination of bowel under Wood lamp illumination can recruit. Resection of necrotic bowel plays an essential role in patient resuscitation while try for anastomosis remains controversial. A second look operation is highly suggested, along with diagnostic imaging and the clinical examination.[72]

•  Revascularization

(1) Embolectomy

Open superior mesenteric artery embolectomy is a good option in patients with indications for open surgical intervention. After midline abdominal incision, the proximal superior mesenteric artery can be visible and palpable. Then with a transverse arteriotomy, the clot can be extracted by a Fogarty embolectomy catheter.[73] In the situation of unsuccessful reperfusion, a mesenteric bypass can be necessary.

(2) Mesenteric bypass

Although SMA revascularization can be performed in several ways, superior mesenteric artery bypass is the common method in acute mesenteric arterial occlusion. Mesenteric bypass perfuses the blood from inflow vessel (such as an iliac artery, aorta, etc.) to the distal of occlusion lesion.[74]

A second-look laparotomy is needed for most patients after mesenteric revascularization for acute mesenteric arterial occlusion to reevaluate the bowel 24 to 48 hours after the initial operation.[75][76]

NOMI or Colonic Ischemia 

Usually, the treatment of NOMI or colonic ischemia focuses on removing insulting factors (vasoconstrictive medications), hemodynamic support and monitoring, treating the underlying cause (sepsis, heart failure), and the administration of intra-arterial vasodilation medications. However, selected patients may require exploratory laparotomy. The colonic ischemia divided into three groups: mild, moderate, and severe ischemia according to the hemodynamic parameters, presence of risk factors, laboratory test results, radiological and colonoscopic findings to guide the treatment.[77] The mild ischemia is defined as a patient with typical symptoms of colonic ischemia but not isolated right colonic lesion and no identifiable risk factor. The moderate ischemia is defined when the patient has up to three of the following factors: male gender, tachycardia (heart rate greater than 100 beats/min), hypotension (systolic blood pressure less than 90 mm Hg), blood urea nitrogen greater than 20 mg/dl, Hgb less than 12 g/dl, LDH greater than 350 U/l, serum sodium less than 136 mEq/l, WBC greater than 15×10/l, abdominal pain without rectal bleeding or colonoscopically identified mucosal ulceration.[78] The severe ischemia is defined by more than three of the previously listed criteria or any of the following: peritoneal signs on abdominal examination, gangrene on colonoscopy, pneumatosis on CT abdomen, and a pan-colonic distribution or isolated right colonic lesion on CT or colonoscopy.[79] The mild ischemia needs only conservative treatment. The moderate ischemia needs broad-spectrum antibiotics and surgical consultation. It is necessary to consider further investigation, such as CTA and colonoscopy, to assess the mesenteric circulation. Severe ischemia requires prompt surgical referral and intensive care unit monitoring.[78]

Differential Diagnosis

The differential diagnosis for bowel ischemia is broad and includes all diseases that can present with abdominal pain. The most common and important diseases can be categorized based on pain localization.

Upper Abdominal Pain

• Gallstones
• Acute cholecystitis/cholangitis
• Hepatitis/perihepatitis/liver abscess
• Epigastric pain
• Pancreatitis
• Peptic ulcer disease
• Gastroparesis

 Lower Abdominal Pain

• Acute appendicitis
• Diverticulitis
• Kidney stone/pyelonephritis
• Infectious colitis

Diffuse Abdominal Pain

• Obstruction
• Inflammatory bowel disease
• Spontaneous bacterial peritonitis
• Cancer (colorectal/gastritis/pancreatic)

Prognosis

The prognosis of intestinal ischemia depends on the underlying mechanism. The mortality rates in acute mesenteric ischemia can exceed 60%.[8] Acute mesenteric venous thrombosis has a better overall mortality rate compared to other forms of acute mesenteric ischemia.[37] Mortality and morbidity in patients with mesenteric venous thrombosis have improved because of better recognition and early treatment.[80] With early diagnosis and anticoagulation treatment, the mortality rates are between 10 to 20%.[81][82] Perioperative mortality in patients with CMI is varied from 0 to 16%, but it can increase up to 50% in patients who develop acute symptoms.[23][83] The prognosis of patients with NOMI or ischemic colitis depends on the etiology, severity, and distribution of the disease.[53] Non-gangrenous colonic ischemia accounts for less than 5% mortality.[71] Patients with colonic necrosis and gangrene have higher mortality rates.[84][85]

Complications

• Bowel infarction and a bowel perforation
• Gangrenous and necrotic bowel
• Sepsis
• Endotoxemia with bacterial translocation
• Toxic megacolon
• Multiple organ failure
• Fibrosis
• Fistula
• Colonic stricture

Consultations

• The interventional radiologist should be consulted for the infusion of papaverine and thrombolytics medications.
• The surgical team should be ready for possible exploratory laparotomy.
• Vascular surgeon consultation is recommended for possible vascular intervention.
• Gastrointestinal doctors should be consulted for the evaluation and diagnosis of the patient.
• Intensive critical unit doctors should be consulted for patient's admission.
• Pharmacist consultation should be ordered for identifying the offending drugs and choosing the preference for medication therapy.

Deterrence and Patient Education

There are various ways the patient can be educated about these diseases, which can prove essential for patient care. In the initial phases, the patients should be informed about the possible ways the disease can present. The understanding of the signs and symptoms from the patients promptly can turn out to be the most crucial factor. Early and timely intervention is the cornerstone in the management, and it can be possible if patients seek care very early when they develop the signs.

Pearls and Other Issues

An interprofessional team member should be aware of the signs and symptoms of intestinal ischemia. Prompt recognition of the disease and early treatment can decrease the morbidity and mortality rate of intestinal ischemia. Severe abdominal pain out of proportion of physical examination should arise acute mesenteric ischemia. In intestinal ischemia, plain x-ray film has limited diagnostic value for the evaluation of AMI.  Laboratory test has limited value for the diagnosis of a patient with intestinal ischemia. CTA should be initial imaging in patients with suspicion of AMI.NOMI should consider in and critically ill patients with abdominal pain who needs pressor support. After the diagnosis of AMI was made, fluid resuscitation, broad-spectrum antibiotics, and anticoagulation medication should be started. Immediate exploratory laparotomy should be performed in patients with peritonitis signs.

Enhancing Healthcare Team Outcomes

Bowel ischemia frequently poses a diagnostic dilemma. These patients may exhibit non-specific signs and symptoms such as vomiting, nausea, and leukocytosis. The cause of bowel ischemia can be due to small intestinal ischemia(known as mesenteric ischemia) and large intestinal ischemia(known as colonic ischemia). Mesenteric ischemia is categorized based on the etiology of ischemia, which includes mesenteric arterial embolism, mesenteric arterial thrombosis, NOMI, mesenteric venous thrombosis, and chronic mesenteric ischemia. While the physical exam may reveal that the patient has a surgical abdomen, the cause is difficult to know without proper imaging studies. While the diagnose of bowel ischemia was made, it is essential to consult with an interprofessional team of specialists that include a general surgeon, vascular surgeon, gastrointestinal physician, interventional radiologist, and intensive care unit physician. The nurses are also vital members of the interprofessional group as they will monitor the patient's vital signs and assist with the education of the patient and family. In the postoperative period for pain, wound infection, and ileus, the pharmacist will ensure that the patient is on the right analgesics, antiemetics, and appropriate antibiotics. Also, Pharmacist consultation should be ordered for identifying the offending drugs and choosing the preference for medication therapy. The radiologist also plays a vital role in determining the cause. Without providing a proper history, the radiologist may not be sure what to look for or what additional radiologic exams may be needed. The American College of Radiology Appropriateness Criteria is evidence-based guidelines for mesenteric ischemia that are reviewed by an interprofessional expert committee. The current guidelines have been developed after an exhaustive review of current medical literature from peer-reviewed journals to determine the appropriateness of radiological imaging and treatment procedures by the committee. The summary of recommendations is as follows. CTA abdomen and pelvis with IV contrast is the recommended initial imaging examination for patients with suspected acute mesenteric ischemia. CTA abdomen and pelvis with IV contrast or MRA abdomen and pelvis without and with IV contrast is recommended as the initial imaging examination in patients with suspected chronic mesenteric ischemia. CTA abdomen and pelvis with IV contrast have been shown to provide the best accuracy and inter-reader agreement for grading mesenteric vessel stenosis compared to MRA and US.[86] [Level 1]