Stephanie A. Taft
Mesenteric ischemia occurs when the blood supply to the small and large intestine is compromised, resulting in insufficient oxygen delivery. While there are different mechanisms for the interruption of normal blood flow, the end result is inadequate perfusion and subsequent cell damage and death. In acute mesenteric ischemia (AMI), delay to diagnosis is the rule rather than the exception (1), resulting in persistently high mortality rates of 40% to 70% despite advances in diagnosis and treatment (2). Other factors affecting mortality are old age, signs of peritonitis, and delays in surgical intervention (3). The clinical presentation is highly variable due to the different vessels involved, the location of the affected bowel, and the different levels of illness severity (4). The most common form of bowel ischemia is ischemic colitis (4), which is a distinct entity described below. Mesenteric ischemia can be acute or chronic and can be further categorized as arterial occlusion, venous occlusion, and arterial nonocclusive disease.
ACUTE MESENTERIC ISCHEMIA
Around 40% to 50% cases of AMI are caused by arterial occlusion due to embolism from the heart or a proximal arterial source (3,5). Thrombosis of atherosclerotic arteries accounts for about 25% of cases (3). Mesenteric venous thrombosis (MVT) is less common, accounting for only 10% to 15% of cases (3) while nonocclusive mesenteric ischemia (NOMI) comprises the remaining 20% to 30% of cases (3,4).
CHRONIC MESENTERIC ISCHEMIA
Chronic mesenteric ischemia (CMI) is commonly caused by the progressive stenosis of multiple atherosclerotic mesenteric blood vessels (5).
CLINICAL PRESENTATION
Acute Mesenteric Ischemia
Patients with AMI secondary to arterial embolism often present with severe abdominal pain with minimal physical signs and usually have a history of cardiovascular disease (5). Nausea, vomiting, and diarrhea are common complaints (1), and stools may be bloody (6). Unfortunately, key findings in AMI are inconsistently present (1), and the nature, location, and duration of the abdominal pain are variable (5), contributing to the delay in diagnosis. As ischemia progresses, peritoneal irritation gives rise to abdominal tenderness (5). Distension, rigidity, and systemic symptoms may take days to develop and correlate with intestinal perforation (5). Later signs also include confusion, tachycardia, tachypnea, and ultimately circulatory collapse due to dehydration and fluid third-spacing (6). Approximately two-thirds of patients with AMI are women, with a median age of 70 (5).
The clinical presentation of patients with AMI secondary to acute thrombosis is similar to that of arterial embolism. However, patients frequently report preceding symptoms of chronic insufficiency such as postprandial abdominal pain, nausea, and weight loss (6). Arterial thrombosis is almost always seen in the setting of severe atherosclerotic mesenteric arterial disease, most commonly near the origin of the superior mesenteric artery (SMA) (5,6). Gradual development of atherosclerotic disease allows development of collaterals, so significant arterial obstruction is often well-tolerated (6). Acute symptoms occur after rupture of a plaque and subsequent occlusion of a normally patent artery or occlusion of an important collateral (6). Ischemia due to acute thrombosis tends to involve larger portions of both small and large intestines, so the extent of bowel ischemia or infarction is greater than that with embolism (6). Ischemia due to acute thrombosis also has higher perioperative mortality due to delays in diagnosis, a greater amount of bowel involved, and the need for more complex revascularization (6).
Patients with acute mesenteric venous thrombosis present with acute, severe midabdominal pain that is out of proportion to physical examination (7). Those with subacute or chronic MVT often present with complications of portal hypertension such as variceal bleeding, and the symptoms may evolve over days to weeks (7). Other symptoms such as nausea, vomiting, and constipation or diarrhea may also occur (7). Ascites in a patient with abdominal pain should heighten suspicion for MVT (7). Causes of MVT include any condition that leads to thrombosis. Examples include inherited or acquired hypercoagulable states (such as Factor V Leiden deficiency, polycythemia vera, malignancy, or oral contraceptive use), or local blood vessel injury (from inflammatory conditions such as pancreatitis or surgery), or from stasis due to conditions such as cirrhosis (7).
NOMI should be suspected in patients who develop abdominal pain or distension in the context of low-flow states or shock, particularly cardiogenic shock, or in patients receiving vasopressors or other vasoconstricting substances, such as cocaine or ergotamine (5). Ischemia occurs without identifiable blood vessel occlusion (3), usually as a result of low-flow states and subsequent severe prolonged vasospasm (5). NOMI is seen most commonly in elderly, critically ill patients. These patients are often intubated and sedated, so the only clue is deterioration of clinical status (6).
Chronic Mesenteric Ischemia
CMI is characterized by postprandial abdominal pain and weight loss which occurs over months to years (5). Patients with CMI often have a history of cardiovascular disease or vascular surgery (5). Because many people who have atherosclerosis of the mesenteric vessels are actually asymptomatic due to collateral circulation (5,9), CMI is diagnosed by demonstration of arterial lesions in the context of abdominal pain, weight loss, history of cardiovascular disease, and no other obvious cause of symptoms (5). Other GI symptoms such as vomiting and diarrhea are uncommon (5). Rare causes include Buerger’s disease, fibromuscular dysplasia, or dissection (5). Some cases progress to AMI while the remainder have progressive weight loss and ultimately die (5).
Ischemic Colitis
Ischemic colitis (IC) is actually the most common form of mesenteric ischemia (4). It is characterized by a sudden onset of mild left lower quadrant abdominal pain followed by mild hematochezia (4). It is most often due to an acute, self-limited compromise of blood flow which is inadequate to meet the metabolic demands of part of the colon. It can be seen in conditions such as congestive heart failure, hypotension, hypovolemia, sepsis, vascular occlusion, vasculitis, or drug use (4,17). The most susceptible areas are the splenic flexure, descending and sigmoid colon, but right-sided (ascending colon) IC is usually associated with more severe colitis and worse outcome (4,18).
DIFFERENTIAL DIAGNOSIS
Mesenteric ischemia is a diagnostic challenge, partly because the differential is extensive and includes nearly any disorder that causes abdominal pain (see Chapter 10), and the physical signs may be nonspecific. While many other conditions are more common than acute ischemia, the incidence of mesenteric ischemia increases with advancing age (10).
ED EVALUATION
Laboratory Testing
There is no sufficiently sensitive or specific serum marker that can identify AMI early (11). The classic findings of elevated lactate, leukocytosis, and acidosis are all insensitive and nonspecific (12). There are also no diagnostic laboratory tests for CMI (5).
Imaging
Contrast-Enhanced Multidetector Computed Tomography
Computed tomography (CT) is the imaging modality of choice in both AMI and CMI (9). CT is able to evaluate the vascular system and the bowel wall and may also identify an alternative etiology (13). In AMI, CT demonstrates a progression of findings, starting with mildly dilated loops of bowel, and a normal or slightly thinned bowel wall (8,13). This is followed by further bowel dilation and progressive thinning of the bowel wall with poor contrast enhancement (13). If reperfusion occurs, the bowel wall thickens due to edema and hemorrhage; however, the bowel wall can still perforate (13). Pneumatosis intestinalis with portomesenteric venous gas often indicates transmural infarction but can also be seen in other conditions, such as inflammatory bowel disease or connective tissue disorders (13). These findings must be interpreted in the correct clinical context and in association with the previously mentioned CT findings suggesting mesenteric ischemia (13). In the absence of other findings of AMI, isolated pneumatosis intestinalis does not necessarily indicate acute ischemia (13). While intravenous (IV) contrast is necessary for CT, oral contrast is neither necessary nor often feasible (13).
In the case of acute MVT, bowel wall thickening is the most common finding, and mesenteric haziness and ascites are also present in most patients (13). In the case of NOMI, CT findings are similar to that of acute arterial occlusive disease but no focal occlusion can be found (13).
Plain Abdominal X-Rays
Plain films are usually nonspecific and do not contribute to diagnosis (5).
Duplex Ultrasound
Ultrasound may be useful in supporting the diagnosis of CMI but has no role in AMI (5). It may be able to identify proximal occlusive lesions but cannot directly diagnose mesenteric ischemia. It also requires ideal exam conditions which include fasting prior to the exam and absence of significant abdominal distension (5,14).
Magnetic Resonance Angiography with Gadolinium
Magnetic resonance angiography is sensitive and specific but generally not readily available and takes too long to perform in a critically ill patient (4,9). It is more useful in diagnosing CMI (5,9,14).
Angiography
Traditional angiography is often diagnostic and may be therapeutic if coupled with endovascular therapy (see below), but it is resource-intensive and not always readily available. Angiography is no longer the gold standard (15).
For patients with ischemic colitis, CT is usually nonspecific but suggestive (4,17). Colonoscopy is the test of choice (17) but is not performed on an emergent basis. Angiography is not indicated (4).
KEY TESTING
• Contrast-enhanced CT.
• Lactate and other basic studies often ordered in the evaluation of abdominal pain.
ED MANAGEMENT
Management in the ED is focused upon resuscitation and basic supportive care. The goal is to minimize the amount of bowel that progresses from ischemia to infarction (5). Appropriate care may include some or all of the following measures depending upon the degree of shock.
Intubation may be necessary for airway protection, oxygenation, or ventilation. Fluid resuscitation should be aggressive, beginning with a bolus of crystalloid. Bedside ultrasound may be useful early on to exclude other pathology such as abdominal aortic aneurysm and to help evaluate the hydration status of the patient. Broad-spectrum IV antibiotics should be administered early, due to the high risk of bacterial translocation across bowel wall (14). If vasopressors are required, pure alpha-adrenergic agents such as phenylephrine should be avoided because they may produce mesenteric vasoconstriction and worsening ischemia (3). Treatment of the underlying shock state is the most important treatment principle in cases of NOMI (5). CT scanning should be accomplished as soon as reasonably possible, given the patient’s condition. Emergent surgical consultation should be obtained, even prior to a definitive diagnosis if the index of suspicion is high or if there are peritoneal findings (3). Anticoagulation should be initiated if there are no contraindications, but this should be done in consultation with the surgeon. In the case of MVT, hematology consultation may be useful to initiate appropriate thrombophilia screening prior to starting anticoagulation (7).
Most patients with ischemic colitis respond within 1 to 2 days to basic supportive care (i.e., bowel rest, IV fluids, empiric antibiotics) (17). In 20% of cases, surgery is required because of deterioration or peritonitis (17).
For patients with chronic ischemia, timely treatment is key for the prevention of acute ischemia (10). Percutaneous endovascular treatment or surgery may be appropriate, depending on the clinical presentation. Recurrence is more common after angioplasty than surgery, but these recurrences can also be treated percutaneously (5). Surgical treatment or revascularization may be accomplished by endarterectomy or bypass grafting (5). Surgery has a good success rate with lower recurrence than percutaneous intervention but has its own associated morbidity and mortality (5).
Beyond the diagnostic and resuscitation issues in the ED, there are several important options and considerations for more definitive care in patients with mesenteric ischemia.
Percutaneous Endovascular Treatment (Angiography)
Angiography may be used for directed lytic therapy, vasodilator (papaverine) therapy, angioplasty, and/or stenting. This modality is evolving into first-line treatment in select patients (1). It is noteworthy that angiography carries a higher risk of reperfusion syndrome than with surgery. Reperfusion syndrome occurs due to the sudden release of endotoxins, resulting in disseminated intravascular coagulation, adult respiratory distress syndrome, and cardiovascular collapse (5).
Surgical Treatment
Laparotomy allows direct visualization and assessment of bowel viability, revascularization (balloon catheter thromboembolectomy or bypass grafting), and resection of infarcted bowel (10). A second operation is often scheduled to re-assess the viability of bowel, avoiding resection of potentially viable bowel during the first operation while allowing further resection of nonviable bowel (5).
CRITICAL INTERVENTIONS
• Fluid resuscitation, may need up to 100 mL/kg (16).
• Broad spectrum IV antibiotics.
• Anticoagulation (in selected cases).
• Surgical consultation.
DISPOSITION
Patients with AMI should be admitted to the hospital and may require surgery. Because the diagnosis is often delayed, these patients are often very sick and require intensive care.
Common Pitfalls
• Allowing a benign abdominal examination to direct the management of a patient with risk factors for AMI. Intervention is most effective when there are few findings on examination.
• Failing to recognize that acute abdominal pain in a patient with a previous diagnosis of CMI is AMI until proven otherwise.
• Relying on a blood gas or serum lactate to rule out mesenteric ischemia. Both are insensitive and become abnormal late in the disease (1).
• Allowing elevation of serum biomarkers to lead to misdiagnosis: elevation of troponin, amylase, lipase, and liver transaminases have all been seen relatively commonly in AMI (1).
• Failing to interpret CT results correctly in the context of a clinical presentation suggestive of AMI. Early mesenteric ischemia can look similar to adynamic ileus on CT (13).
REFERENCES
1. Acosta S, Block T, Bjornsson S, et al. Diagnostic pitfalls at admission in patients with acute superior mesenteric artery occlusion. J Emerg Med. 2012;42(6):635–641.
2. Kassahun WT, Schulz T, Richter O, et al. Unchanged high mortality rates from acute occlusive intestinal ischemia: Six year review. Langenbecks Arch Surg. 2008;393:163–171.
3. Lewiss RE, Egan DJ, Shreves A. Vascular abdominal emergencies. Emerg Med Clin North Am. 2011;29:253–272.
4. Sreenarasimhaiah J. Diagnosis and management of intestinal ischaemic disorders. BMJ. 2003;326:1372–1376.
5. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic). Circulation. 2006;113:e463–e654.
6. Oldenburg W, Lau L, Rodenberg TJ, et al. Acute mesenteric ischemia: A clinical review. Arch Intern Med. 2004;164(10):1054–1062.
7. Singal AK, Kamath PS, Tefferi A. Mesenteric venous thrombosis. Mayo Clin Proc. 2013;88:285–294.
8. Horton KM, Fishman EK. CT angiography of the mesenteric circulation. Radiol Clin North Am. 2010;48:331–345.
9. Upponi S, Harvey JJ, Uberoi R, et al. The role of radiology in the diagnosis and treatment of mesenteric ischemia. Postgrad Med J. 2013;89:165–172.
10. Park WM, Gloviczki P, Cherry KC, et al. Contemporary management of acute mesenteric ischemia: Factors associated with survival. J Vasc Surg. 2002;35: 445–452.
11. Demir IE, Ceyhan GO, Friess H. Beyond lactate: Is there a role for serum lactate measurement in diagnosing acute mesenteric ischemia? Dig Surg. 2012; 29:226–235.
12. Evennett NJ, Petrov MS, Mittal A, et al. Systematic review and pooled estimates for the diagnostic accuracy of serological markers for intestinal ischemia. World J Surg. 2009;33:1374–1383.
13. Lee SS, Park SH. Computed tomography evaluation of gastrointestinal bleeding and acute mesenteric ischemia. Radiol Clin North Am. 2013;51:29–43.
14. van den Heijkant TC, Aerts BA, Teijink JA, et al. Challenges in diagnosing mesenteric ischemia. World J Gastroenterol. 2013;19(9):1338–1341.
15. Cangemi JR, Picco MF. Intestinal ischemia in the elderly. Gastroenterol Clin North Am. 2009;38:527–540.
16. Lock G. Acute intestinal ischaemia. Best Pract Res Clin Gastroenterol. 2001;15: 1583–1598.
17. Green BT, Tendler DA. Ischemic colitis: A clinical review. South Med J. 2005; 98(2):217–222.
18. Theodoropoulou A, Koutroubakis. Ischemic colitis: Clinical practice in diagnosis and treatment. World J Gastroenterol. 2008;14(48):7302–7308.