Improving the ED Diagnosis of Mesenteric Ischemia

Authors: Angela G. Cai, MD, MBA (EM Resident Physician, SUNY Downstate Health Sciences University/Kings County Hospital, @angelagcai) and Ian S. deSouza, MD (Professor of Emergency Medicine SUNY Downstate Health Sciences University/Kings County Hospital) // Reviewed by Mark Ramzy, DO (@MramzyDO); Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Case 1: A 75-year-old female with chronic atrial fibrillation presents with severe, sudden abdominal pain and nausea. She has normal vital signs, appears very uncomfortable, and has mild, diffuse abdominal tenderness.

This is your textbook case of mesenteric ischemia, but often the patient will not present this way. Mesenteric ischemia remains a high mortality and easily missed diagnosis in emergency medicine. A rare disease accounting for fewer than 1 in 1000 hospital admissions, it develops as a result of insufficient mesenteric blood flow to the visceral organs. Mesenteric ischemia rises from various etiologies that involve thromboembolic occlusion or non-occlusive supply and demand mismatch. Prompt diagnosis significantly improves mortality with one study showing a mortality drop from 70% to 14% when time to diagnosis decreases from 24 to 12 hours.¹ This post will discuss when to raise your index of suspicion for this disease and how to avoid missed or delayed diagnosis.

The Diagnostic Challenges

Mesenteric ischemia presents with variable and nonspecific history, exam, and laboratory findings. Typical history and physical exam findings are not reliably present. As little as 60% may report abdominal pain, 45% display pain out of proportion to exam, and only 3% demonstrate peritonitis (Figure 1).² Visceral abdominal pain develops as the intestinal mucosa becomes ischemic, being furthest from the blood supply and therefore most vulnerable. Only when the outer muscularis and serosa layers become ischemic does peritonitis develop.³ As a result, the patient may initially have abdominal pain out of proportion to tenderness. Patients may even have a three to 6-hour pain-free interval due to hypoperfusion of pain receptors.³ The exact constellation of symptoms and acuity of the presentation also depend on the specific etiology. Mesenteric ischemia ultimately requires computed tomography angiography (CTA) abdomen and pelvis to rule out.

How to Improve the Diagnosis

1. Know the risk factors and diverse presentations by etiology.

While all etiologies of mesenteric ischemia converge on the process of bowel ischemia, the underlying pathophysiology, and therefore, risk factors and presentation vary across four major categories. Understanding these general presentations of mesenteric ischemia will aid in recognition despite the variation (Table 1).⁴ We will explore this variation with a typical case presentation of each etiology, starting with our first patient.

Back to Case 1: A 75-year-old female with chronic atrial fibrillation presents with severe, sudden abdominal pain with ‘pain out of proportion’ to tenderness on exam 

Arterial embolism accounts for the majority of cases of mesenteric ischemia with half occurring at the superior mesenteric artery (SMA) supplying the midgut (distal duodenum to the splenic flexure).⁸ Less frequently, emboli may occlude the celiac artery supplying the foregut (distal esophagus to proximal duodenum) or the inferior mesenteric artery (IMA) supplying the hindgut (splenic flexure to distal sigmoid). Patients with arterial embolism commonly have atrial fibrillation and present more acutely with the classic “pain out of proportion”.⁸

Case 2: A 68-year-old male with coronary artery disease, diabetes, hypertension, hyperlipidemia presents with several hours of constant, diffuse abdominal pain that began after eating dinner, similar but more persistent than past episodes. His exam reveals diffuse tenderness with rebound.

Arterial thrombosis in the setting of chronic atherosclerosis may present with similar acuity or a more progressive onset depending on the preexisting vessel disease and collateral flow. Patients with chronic mesenteric ischemia almost always report a prior history of postprandial abdominal pain. This pain represents intestinal angina which develops when the demand for blood flow for digestion exceeds the capacity of obstructed mesenteric arteries to supply the intestinal mucosa. Total mesenteric blood flow represents 20% of resting cardiac output and can increase up to two times postprandially.⁸ Chronic ischemia frequently results in weight loss, nausea, and vomiting.⁸

Case 3: A 55 year-old female with ESRD and CHF on vasopressors for septic shock has an episode of bloody diarrhea.

Nonocclusive arterial mesenteric ischemia results from inadequate supply of blood due to an underlying critical illness and most commonly affects the descending or sigmoid colon.⁸ Bowel can tolerate a 75% reduction in blood flow for up to 12 hours through multiple adaptations: increasing oxygen extraction (up to 90%), autoregulation of arterial resistance, and capillary recruitment (bowel utilizes only 25% of intestinal capillaries at rest).⁹ Colonic ischemia may present as bleeding, pain, or perforation with peritonitis. The diagnosis may be complicated by limited history due to critical illness or mechanical ventilation.^8,10 The literature has distinguished between mesenteric ischemia and ischemic colitis in reference to ischemia of the small bowel (SMA) versus colon (IMA), respectively.^11,12 Recent reviews differentiate mesenteric ischemia by etiology (e.g. occlusive versus nonocclusive) rather than region of ischemia.^1,5,6,10 Additionally, SMA supply of the colon and variations in vascular anatomy may render this distinction less clinically useful.

Case 4: 30 year-old female with a history of deep venous thrombosis presents with constant upper abdominal pain worsening over 2 days and a normal exam.

Mesenteric vein thrombosis presents more insidiously with vague abdominal pain usually for greater than 24 hours and even one month from onset. Risk factors include hypercoagulability as seen in malignancy, sepsis, liver disease, portal hypertension, sickle cell disease, and inherited thrombophilias. Anticoagulation with heparin and transition to oral medication is the mainstay of treatment rather than surgical or endovascular intervention.^3,5

2. Have the clinical suspicion, and tell your radiologist.

Clinicians must actively maintain suspicion so as not to overlook this rare but fatal diagnosis. The degree to which test results, such as CTA findings, changes the likelihood of a disease depends on a patient’s pre-test probability. Pre-test probability depends on clinical suspicion and prevalence of a disease.¹³ If a radiologist is not informed of clinical suspicion for mesenteric ischemia, they may not attribute clinical significance to subtle and nonspecific radiologic findings often seen in mesenteric ischemia (Tables 2 and 3). Furthermore, rate of successful diagnosis may improve if clinical suspicion is communicated in the radiology referral.¹⁰

3. Raise your clinical suspicion in the elderly.

Although a rare diagnosis overall, mesenteric ischemia appears significantly more commonly in the elderly.¹⁰ Incidence rate can be understood as the risk of developing a disease over a relevant time period. (The relevant time period includes the time during which a patient is ‘at-risk’ of developing the disease. If the patient develops the disease or dies, for example, they no longer contribute to the incidence rate calculation).¹⁵ In a retrospective, single-center analysis of a well-defined Finnish population, inhabitants older than 75 years had an incidence rate (cases/100,000 persons/year) of 51.2 for mesenteric ischemia compared to 40.2 for acute appendicitis. For point of reference, the incident rate of acute appendicitis among inhabitants 75 years or younger was 92.1.¹⁰ Figure 2 illustrates the exponential rise in incidence rate of acute mesenteric in the elderly compared to other acute abdominal pathologies.

4. Get the CTA and do not rely on the labs.

CTA of the abdomen and pelvis is the preferred diagnostic imaging modality for suspected mesenteric ischemia due to its speed, noninvasiveness, and high accuracy (93-100% sensitivity and specificity).¹⁶ Imaging involves thin-section acquisition timed with arterial or venous enhancement and three dimensional rendering. A noncontrast phase, without intravenous or oral contrast enhancement, although not required, may help identify intramural hemorrhage, atherosclerotic calcifications, and establish baseline wall enhancement. CTA of the abdomen and pelvis can detect vascular and nonvascular signs of mesenteric ischemia as well as exclude alternate causes of abdominal pain (Figure 3-4).¹⁶ In one study of 959 patients suspected to have mesenteric ischemia, 19% of patients had the disease, 20% had no clear diagnosis, and 61% had specific alternate diagnoses; small bowel obstruction, infectious colitis, pneumonia, cholecystitis, and diverticulitis accounted for one-third of alternate diagnoses.¹⁷

No laboratory parameters have demonstrated adequate performance for the diagnosis of mesenteric ischemia. Biomarkers studied include those of oxidative stress (e.g. lactate), inflammation or infection (e.g. leukocytosis), and novel markers of wall damage (e.g. intestinal fatty acid binding protein [I-FABP]). Notably, D-dimer’s high sensitivity may suggest its use as a rule-out test (sensitivity 0.94, specificity 0.40). Most studies have significant limitations including small study populations and heterogeneous methods and reference standards.^20,21

Take-aways for your practice

Mesenteric ischemia continues to challenge emergency physicians with its subtle and variable presentations. Accurate and timely diagnosis significantly improves mortality in this deadly disease. Strategies to avoid missing the diagnosis include recognizing the presentations of the four main etiologies (arterial embolism, arterial thrombosis, nonocclusive, venous thrombosis), maintaining a high index of suspicion and communicating this to the radiologist, raising your clinical suspicion in the elderly, and relying only on CTA to rule out the diagnosis.

References and Further Reading:

1. Carver TW, Vora RS, Taneja A. Mesenteric Ischemia. Crit Care Clin. 2016;32(2):155-171. PMID: 27016159
2. Cudnik MT, Darbha S, Jones J, Macedo J, Stockton SW, Hiestand BC. The diagnosis of acute mesenteric ischemia: A systematic review and meta-analysis. Acad Emerg Med. 2013;20(11):1087-1100. PMID: 24238311
3. Singh M, Long B, Koyfman A. Mesenteric Ischemia: A Deadly Miss. Emerg Med Clin North Am. 2017;35(4):879-888. PMID: 28987434
4. Mesenteric Ischemia: A Power Review – emDOCs.net – Emergency Medicine Education. emDOCs.net – Emergency Medicine Education. http://www.emdocs.net/mesenteric-ischemia-power-review/. Published November 12, 2014. Accessed June 24, 2020.
5. Clair DG, Beach JM. Mesenteric Ischemia. N Engl J Med. 2016;374(10):959-968. PMID: 26962730
6. Gnanapandithan K, Feuerstadt P. Review Article: Mesenteric Ischemia. Curr Gastroenterol Rep. 2020;22(4):17. PMID: 32185509
7. Brandt LJ, Feuerstadt P, Longstreth GF, Boley SJ, American College of Gastroenterology. ACG clinical guideline: epidemiology, risk factors, patterns of presentation, diagnosis, and management of colon ischemia (CI). Am J Gastroenterol. 2015;110(1):18-44; quiz 45. PMID: 25559486
8. Sise MJ. Acute mesenteric ischemia. Surg Clin North Am. 2014;94(1):165-181. PMID: 24267504
9. Al-Diery H, Phillips A, Evennett N, Pandanaboyana S, Gilham M, Windsor JA. The Pathogenesis of Nonocclusive Mesenteric Ischemia: Implications for Research and Clinical Practice. J Intensive Care Med. 2019;34(10):771-781. PMID: 30037271
10. Kärkkäinen JM, Acosta S. Acute mesenteric ischemia (part I)-–Incidence, etiologies, and how to improve early diagnosis. Best Pract Res Clin Gastroenterol. 2017;31(1):15-25. PMID: 28395784
11. Ischemic Colitis: ED Presentations, Evaluation, and Management – emDOCs.net – Emergency Medicine Education. emDOCs.net – Emergency Medicine Education. http://www.emdocs.net/ischemic-colitis-ed-presentations-evaluation-and-management/. Published December 9, 2019. Accessed June 23, 2020.
12. Lewiss RE, Egan DJ, Shreves A. Vascular abdominal emergencies. Emerg Med Clin North Am. 2011;29(2):253-272, viii. PMID: 21515179
13. Pellatt R, Purdy E, Keijzers G. Review article: A primer for clinical researchers in the emergency department: Part XI. Inertia before investigation: Pre-test probability in emergency medicine. Emerg Med Australas. 2020;32(3):377-382. PMID: 32367641
14. Olson MC, Fletcher JG, Nagpal P, Froemming AT, Khandelwal A. Mesenteric ischemia: what the radiologist needs to know. Cardiovasc Diagn Ther. 2019;9(Suppl 1):S74-S87. PMID: 31559155
15. Boston University School of Public Health. Incidence: Risk, Cumulative Incidence (Incidence Proportion), and Incidence Rate. MPH Online Learning Modules. https://sphweb.bumc.bu.edu/otlt/MPH-Modules/EP/EP713_DiseaseFrequency/EP713_DiseaseFrequency4.html. Published November 1, 2016. Accessed June 27, 2020.
16. Ginsburg M, Obara P, Lambert DL, et al. ACR Appropriateness Criteria® Imaging of Mesenteric Ischemia. J Am Coll Radiol. 2018;15(11, Supplement):S332-S340. PMID: 30392602
17. Henes FO, Pickhardt PJ, Herzyk A, et al. CT angiography in the setting of suspected acute mesenteric ischemia: prevalence of ischemic and alternative diagnoses. Abdom Radiol (NY). 2017;42(4):1152-1161.PMID: 30999055
18. Hidayatov A. Pulmonary embolism with superior mesenteric artery thrombosis | Radiology Case | Radiopaedia.org. Radiopaedia. https://radiopaedia.org/cases/pulmonary-embolism-with-superior-mesenteric-artery-thrombosis?lang=us. Accessed July 13, 2020.
19. Gaillard F. Ischemic small bowel | Radiology Case | Radiopaedia.org. Radiopaedia. https://radiopaedia.org/cases/ischemic-small-bowel. Accessed July 13, 2020. PMID: 30306080
20. Khan SM, Emile SH, Wang Z, Agha MA. Diagnostic accuracy of hematological parameters in Acute mesenteric ischemia-A systematic review. Int J Surg. 2019;66:18-27. PMID: 30999055
21. Montagnana M, Danese E, Lippi G. Biochemical markers of acute intestinal ischemia: possibilities and limitations. Ann Transl Med. 2018;6(17):341. PMID: 30306080