The Dangerous Miss: Recognizing Acute Mesenteric Ischemia

80% of acute mesenteric ischemia cases result in mortality because of missed diagnosis. Here’s how to recognize the signs.

The shift has just started, and your view of the waiting room reveals several patients with abdominal pain who checked in within twenty minutes of each other. The first patient is a 32 year-old female who presents with one week of worsening abdominal pain, which is non-localized. She has no medical problems, takes only oral contraceptives, and has a family history of venous thromboembolism. Her physical exam is normal, including vital signs, but she continues to complain of severe pain. You order a CBC, liver function panel, basic metabolic panel, urinalysis, and urine pregnancy test, while also ordering medications for nausea and pain. Your second patient is a 53 year-old male presenting with abdominal pain that worsens with eating and lasts several hours. He has no desire to eat due to worsening pain with food. He has a history of hypertension, peripheral vascular disease (PVD), chronic tobacco use, and diabetes. His exam is normal with no tenderness to palpation.

Most physicians know the classic story of mesenteric ischemia, such as the 77 year-old male with a history of coronary disease, atrial fibrillation, coronary bypass, and hypertension who presents with severe abdominal pain but normal physical exam. However, acute mesenteric ischemia (AMI) does not always present so classically, and missing the diagnosis is associated with mortality rates approaching 80% [1]. The wide variety of presentations and symptoms of this disease creates a diagnostic challenge [2].

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Background
Abdominal vascular catastrophes are uncommon but can be fatal. Acute mesenteric ischemia (AMI) is one abdominal catastrophe of great interest to emergency physicians in that rapid diagnosis and initiation of treatment can prevent mortality and reduce long-term morbidity. The often quoted “Time is bowel” is a sentiment that speaks to the danger of this disease and need for diagnosis [3].

The annual incidence of this disease is 0.09-0.2% per year and ~1% of acute abdomen hospitalizations, but this rarity is offset with a 60-80% mortality within the first 24 hours especially if the disease is missed [4,5]. With the population around the world growing older, this incidence is increasing. Unfortunately this disease presents with a variety of nonspecific symptoms that overlap with other diseases, creating challenges even for the most astute clinician.

The Classic Types
There are four types of AMI, which include arterial embolism (AE), arterial thrombosis (AT), venous thrombosis, and non-occlusive (NOMI). Originally it’s thought arterial embolism is most common, but now studies demonstrate approximately equal rates of arterial thrombosis and embolism (40%) [6]. The four etiologies are shown in table 1 (below), with symptoms, presentation, risk factors, incidence, and mortality.

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Click image to enlarge

Clinical Presentation
As shown in Table 1, symptoms and presentations are nonspecific, which can provide a false sense of security. The symptoms and presentation vary based on the type and etiology of the disease [1,3,7]. The typical presentation is an elderly patient (median age 74 years) with multiple comorbidities who presents with “pain out of proportion” to exam, meaning the patient is experiencing intense pain, while there is little to no tenderness on palpation [1,3,7]. Risk factors including peripheral arterial disease (27%), coronary artery disease (46%), diabetes, and hypertension are common, but not always present [8-10].

Pain is the most consistent symptom, which begins with cramping, periumbilical pain due to small bowel ischemia, which evolves into tenderness to palpation with transmural ischemia of the bowel wall. If necrosis occurs, diffuse peritonitis and sepsis may result [7,11,12]. This is due to infarction of all bowel layers, causing diffuse pain to palpation. However, peritonitis is reported in only 16% of patients with necrotic bowel [13].

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Other early symptoms including vomiting, diarrhea, distension, and bloody stool are common, but not always present. The early vomiting and diarrhea are due to bowel ischemia, causing “gut-emptying.” Bowel sounds are not helpful in ruling in or out the disease [14] and several studies have demonstrated that abnormal mental status can also be associated with presentation [7,11,12]. Presentation truly varies based on the etiology and type of AMI [1,4,7]. These findings including acute abdominal pain, pain out of proportion, peritoneal signs, guaiac-positive stool, heart failure, and atrial fibrillation possess a wide range of sensitivities and are frequently absent [1,7,15]. This wide variety of presentations and large variability in range of performance characteristics of the history and physical examination underlines the diagnostic challenge. Presentation and exam are challenging, as one study demonstrates the disease is suspected in only 22% of patients [7]! The key to diagnosis is evaluating risk factors such as critical illness, comorbidities (hypertension, diabetes, PAD), dialysis, VTE history and considering this disease in the differential. Pain out of proportion, seen in necrotizing fasciitis and compartment syndrome, must be considered a red flag and trigger the physician to consider deadly diagnoses. The patient with minimal tenderness on palpation but severe, intense pain requires consideration for AMI.

Investigations
When considering the disease, what tests can assist in diagnosis? Laboratory tests include white blood cell count (WBC), pH, D-dimer, lactate, and urine intestinal fatty acid binding protein (I-FABP). Many providers rely on these tests to enhance diagnosis. However, this is a pitfall. Approximately 75% of patients will have a WBC greater than 15,000 cells/mm3 [13]. However, this does not differentiate AMI from other diagnoses, and 25% of cases do not have an elevation! Metabolic acidosis is not always present, and metabolic alkalosis can present early if vomiting is a predominant symptom [5]. The D-dimer is sensitive at 96%, but as usual, it is not specific. Providers also rely on elevated lactate for diagnosis. However, this test is not always elevated. Early in the disease process, lactate is normal as it travels through the portal venous system to the liver, where it is converted into glucose. As gut ischemia increases, the liver is unable to keep up with converting lactate into glucose, and lactate spills over into the blood [1,7,15]. A newer test includes urine I-FABP, with a sensitivity of 90% and specificity of 89% in one study. However, these findings have not been validated, and the vast majority of EDs do not have access to this test [5,16]. A summary of laboratory test sensitivity and specificity is demonstrated in Table 2.

With the large range of symptoms and no gold standard laboratory test, imaging is required. With today’s imaging, CT angiography of the abdomen and pelvis with IV contrast is most commonly used [21-23]. Sensitivity of the new multidetector row technology CT angiography (MDRCT) is 95%, with specificity of 95% in one meta-analysis [7]. However, this test can miss 5% of patients. MDRCT angiography identifies mucosal ischemia and small perfusion defects missed with traditional angiography.

Abdominal plain films are normal in 25% of cases, and the classic thumb printing, pneumatosis, free air, portal venous gas are only present with transmural ischemia and bowel necrosis (40%). Do not rely on a normal xray to rule out disease [12,17]. Ultrasound (US) can detect greater than 50% stenosis in chronic mesenteric ischemia, but its use in AMI is limited due to distended bowel. However, this test may reveal signs of obstruction [1,18]. Magnetic resonance angiography (MRA) lacks CT resolution, overestimates degree of stenosis, and takes longer to obtain [19]. Angiography was the gold standard imaging modality, but now its primary use is for patients whose CT is not conclusive. Angiography does play a role in treatment as catheter-based therapy and vasodilation treatment are cornerstones of management, especially in those patients deemed too risky for open surgical techniques [1,5,19]. In addition, patients who undergo successful revascularization procedures may still require intra-arterial vasodilators to treat associated vasospasm [1,5,20].

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Laparoscopy can be used if the prior tests are unrevealing. Studies have shown that the mean time between admission and diagnostic laparoscopy (10.2 hours) was significantly shorter in patients who underwent successful revascularization and in those who survived with or without developing short bowel syndrome [24].

Anatomy and Pathogenesis
The abdominal aorta provides three branches to the intestines, shown in Figure 1 (below). The first branch is the celiac artery, which provides blood to the distal esophagus to second portion of duodenum. AMI is rare to this area due to short, wide artery and collateral flow. The second branch is the superior mesenteric artery, which perfuses the duodenum to distal transverse colon. This artery is most commonly affected in embolism with a 45° angle take-off. Finally, the inferior mesenteric artery perfuses the transverse colon to rectum. It is rarely the sole vessel involved in MI. Collateral circulation from the CA or IMA generally allows sufficient perfusion in reduced SMA occlusion states, such as NOMI or thrombotic mesenteric ischemia. However, occlusion of a single vessel, usually in the setting of embolus, can result in marked ischemia [1,4,12,25].

Bowel wall innervation explains the presentation and symptoms of affected patients. In early disease stages, the mucosal layer becomes ischemic, as it’s the furthest from vascular supply. The pain will be visceral in nature. Eventually, the muscularis and serosal layers become ischemic, leading to peritoneal irritation and guarding with rigidity. At this point, the pain is “in proportion” to the exam. However, there can be a deceptive pain-free interval of 3-6 hours caused by a decline in intramural pain receptors from hypoperfusion. The patient may present with intense pain with minimal findings, which then improves. Once transmural infarction occurs, pain will recur [3,4,12]. Translocation of bacteria from the lumen of the intestine follows infarction [1,3,4,7].

Treatment
The key to management is initiation of treatment while diagnostic evaluation is underway. Optimal treatment requires a multidisciplinary approach: general surgery, vascular surgery, and interventional radiology. Surgical intervention that can be initiated in less than six hours from symptom onset adds significant increase in survival [1,4,26,27]. Three principles guide the surgical management of thromboembolic AMI: SMA revascularization, assessment of intestinal viability, and resection of necrotic bowel. Surgeons can utilize open or endovascular repair. If peritonitis is present, this obviates the need for further testing if you are considering AMI. Instead, speak with surgery about your findings and concern for transmural infarction.

What can emergency physicians do besides calling for help? Aggressive fluid resuscitation, electrolyte management, and broad-spectrum antibiotics are needed early in the course [28]. Avoid oral intake, which can exacerbate ischemia. Patients may require 10-20 L of IV fluids within the first 24 hours due to extensive capillary leakage and third spacing. Begin anticoagulation in consultation with the treating surgeon, usually with unfractionated heparin [4,14,19,29]. Vasospasm is common and can be treated with intra-arterial papaverine infusion, but this requires angiography [28]. Another option is the vasodilator prostaglandin E1 (PGE1) which is administered intravenously [30].

Outcomes
Mortality was 80% as reported in 1999, but true mortality varies based on cause [1,31]. As discussed previously, early diagnosis saves lives. Beaulieu and colleagues showed a 70% mortality if time to diagnosis was more than 24 hours versus a 14% mortality if less than 12 hours [10,24]. Complications following treatment of AMI, such as respiratory failure, multi-organ system failure, sepsis, and short gut syndrome, affect 35% to 79% of patients [8,32]. These patients will require intensive care monitoring due to the high propensity of complications.

Conclusions
Let’s go back to our two patients: the 32 year-old female with worsening abdominal pain and 53 year-old male with “food fear,” both with minimal to no tenderness on exam but severe pain. You have given both patients IV pain and nausea medication, but their pain has continued. You order a CT angiography for both. The radiologist calls back with the results, and he has done you a huge favor by speaking with the interventional radiologist and the general surgeon on call. The 32 year-old female has mesenteric venous thrombosis of the superior mesenteric vein extending into the splenic vein. The 53 year-old male has diffuse mesenteric vascular thrombotic disease involving the origins of the superior mesenteric and inferior mesenteric arteries. You speak with the general surgeon while ordering broad-spectrum antibiotics and IV fluids. The surgeon will contact the ICU physician, and he will be calling his operative nurse as well.

In summary, AMI has four etiologies: AE, AT, venous thrombosis, and NOMI. AE and AT have equal incidences, approximately 40%. No history or physical examination finding can definitively diagnose the condition, but a wide variety of presentations occur, which creates the diagnostic challenge. Pain out of proportion and gut emptying may occur early in the disease, with minimal tenderness on exam. Once transmural infarction occurs, peritoneal findings and tenderness to palpation may occur. Be suspicious of pain out of proportion and scrutinize risk factors (critically ill, PVD, CAD, ESRD, dialysis, and hypercoagulable states). Remember, CT angiography is the best imaging modality. Laboratory findings do not have sufficient sensitivity and specificity for ruling out or in the disease. Lactate may not be elevated early in the disease course, and 25% of the time no elevated WBC will be found. Treatment requires surgery and interventional radiology consultation, IV antibiotics, IV fluids, and anticoagulation. Ultimately, the physician at the bedside is the best diagnostic tool.

REFERENCES

1. Lewiss RE, Egan DJ, Shreves A. Vascular Abdominal Emergencies. Emerg Med Clin N Am 2011;29:253-272.
2. McKinsey JF, Gewertz BL. Acute mesenteric ischemia. Surg Clin North Am 1997;77:307-18.
3. Martinez JP, Hogan GJ. Mesenteric ischemia. Emerg Med Clin N Am 2004;22(4): 909-928.
4. Sise MJ. Acute mesenteric ischemia. Surg Clin North Am 2014;94(1):165-181.
5. van den Heijkant TC, et al. Diagnosis of mesenteric ischemia. World J Gastroenterol 2013;19(9):1338-1341.
6. Meyers SI. Acute embolic and thrombotic mesenteric ischemia. In: Stanley J, Vieth F, Wakefield T, editors. Current Therapy in Vascular and Endovascular Surgery. 5th ed. Philadelphia: Elsevier; 2014. p. 718–20.
7. Cudnik MT, Darbha S, Jones J, et al. The diagnosis of acute mesenteric ischemia: a systematic review and meta-analysis. Acad Emerg Med 2013;20:1087–100.
8. Dahlke MH, Asshoff L, Popp FC, et al. Mesenteric ischemia–outcome after surgical therapy in 83 patients. Dig Surg 2008;25:213–9.
9. Marchena-Gomez J, Acosta-Merida MA, Hemmersbach-Miller M, et al. The age adjusted Charlson Comorbidity Index as an outcome predictor of patients with acute mesenteric ischemia. Ann Vasc Surg 2009;23:458–64.
10. Beaulieu RJ, Arnaoutakis KD, Abularrage CJ, et al. Comparison of open and endovascular treatment of acute mesenteric ischemia. J Vasc Surg 2014;59:159–64.
11. Burns BJ, Brandt LJ. Intestinal ischemia. Gastroenterol Clin North Am 2003;32:1127–43.
12. Oldenburg WA, Lau LL, Rodenberg TJ, et al. Acute mesenteric ischemia: a clinical review. Arch Intern Med 2004;164:1054–62.
13. Acosta S, Block T, Bjornsson S, et al. Diagnostic pitfalls at admission in patients with acute superior mesenteric artery occlusion. J Emerg Med 2012;42:635–41.
14. Bobadilla JL. Mesenteric ischemia. Surg Clin North Am 2013;93:925–40, ix.
15. Cohn, Brian. Does This Patient Have Acute Mesenteric Ischemia?. Ann Emerg Med 2014;64(5):533-534.
16. Thuijls G, van Wijck K, Grootjans J, et al. Early diagnosis of intestinal ischemia using urinary and plasma fatty acid binding proteins. Ann Surg 2011;253:303–8.
17. McCarthy E, Little M, Briggs J, et al. Radiology and mesenteric ischaemia. Clin Radiol 2015;70:698–705.
18. Schwartz LB, Ng TT, McKinsey JF, et al. Diagnosis and surgical management of the visceral ischemic syndromes. In: Moore W, editor. Vascular and Endovascular Surgery. 8th ed. Philadelphia: Saunders; 2013. p. 423–36.
19. Wyers MC. Acute mesenteric ischemia: diagnostic approach and surgical treatment. Semin Vasc Surg 2010;23:9–20.
20. Stone JR, Wilkins LR. Acute Mesenteric Ischemia. Tech Vasc Interventional Rad 2015;18:24-30.
21. Aschoff AJ, Stuber G, Becker BW, Hoffmann MH, Schmitz BL, Schelzig H, Jaeckle T. Evaluation of acute mesenteric ischemia: accuracy of biphasic mesenteric multidetector CT angiography. Abdom Imaging 2009;34:345-57.
22. Ofer A, Abadi S, Nitecki S, et al. Multidetector CT angiography in the evaluation of acute mesenteric ischemia. Eur Radiol 2009;19:24-30.
23. Renner P, Kienle K, Dahlke MH, et al. Intestinal ischemia: current treatment concepts. Langenbecks Arch Surg 2011;396:3–11.
24. Gonenc M, Dural CA, Kocatas A, et al. The impact of early diagnostic laparoscopy on the prognosis of patients with suspected acute mesenteric ischemia. European Journal of Trauma and Emergency Surgery 2013;39(2):185-189.
25. Walker TG. Mesenteric vasculature and collateral pathways. Semin Intervent Radiol 2009;26:167–74.
26. Eltarawy IG, Etman YM, Zenati M, et al. Acute mesenteric ischemia: the importance of early surgical consultation. Am Surg 2009;75:212–9.
27. Ryer EJ, Kalra M, Oderich GS, et al. Revascularization for acute mesenteric ischemia. J Vasc Surg 2012;55:1682–9.
28. Kozuch PL, Brandt LJ. Review article: diagnosis and management of mesenteric ischaemia with an emphasis on pharmacotherapy. Aliment Pharmacol Ther 2005;21:201–15.
29. Frishman WH, Novak S, Brandt LJ, et al. Pharmacologic management of mesenteric occlusive disease. Cardiol Rev 2008;16:59–68.
30. Mitsuyoshi A, Obama K, Shinkura N, et al. Survival in nonocclusive mesenteric ischemia: early diagnosis by multidetector row computed tomography and early treatment with continuous intravenous high-dose prostaglandin E(1). Ann Surg 2007;246:229–35.
31. Schoots IG, Koffeman GI, Legemate DA, et al. Systematic review of survival after acute mesenteric ischaemia according to disease aetiology. Br J Surg 2004;91:17–27.
32. Kougias P, Lau D, El Sayed HF, et al. Determinants of mortality and treatment 
outcome following surgical interventions for acute mesenteric ischemia. J Vasc Surg 2007;46:467–74.