Chronic Mesenteric Ischemia: A Curable Cause of Failure to Thrive
Chronic mesenteric ischemia (CMI) has been described as “episodic or constant intestinal hypoperfusion, resulting from a blood supply insufficient to satisfy the metabolic demands of postprandial bowel activity.”1 CMI, which the literature sometimes refers to as chronic splanchnic syndrome, is relatively rare and accounts for only 5% of all intestinal ischemic events.2 Approximately 95% of patients with CMI have diffuse atherosclerosis, considered the most common cause of CMI.3,4 Patients with conditions that predispose them to atherosclerosis, such as hypertension, diabetes mellitus, and hypercholesterolemia, are at increased risk for CMI,3 and this may partially explain why the prevalence of CMI increases with age.
Due to CMI’s nonspecific symptoms, it is often diagnosed late in the course of the illness, once it has started to impair patients’ functional ability.5 Prior to diagnosis, most patients lose an average of 20 to 30 lb6 and, based on their clinical picture, are initially thought to have a malignancy. Many are given a diagnosis of failure to thrive. Left untreated, CMI can have life-threatening consequences, such as severe malnutrition, bowel infarction, perforation, and sepsis.3,4
We discuss two contrasting cases of CMI involving elderly women. Before their diagnosis, both women experienced significant weight loss and a marked decline in their level of physical activity. The two cases were managed differently and had vastly different outcomes. The significant physical deterioration evident in these patients prior to diagnosis illustrates why CMI should be included in the differential diagnosis of older adults who present with failure to thrive.
Case 1
An 82-year-old white woman with type 2 diabetes mellitus, peripheral artery disease, and hypertension presented with a 2-month history of abdominal pain and postprandial bloating and vomiting, but no constipation or diarrhea. She reported that her symptoms began within an hour after beginning a meal and would resolve a few hours after eating. Because of her symptoms, she had resorted to eating small meals of crackers and soup, which provided partial symptom relief, but led to rapid weight loss. She was not a smoker and had been active and in good health prior to symptom onset, swimming 5 days every week. Afterward, she started swimming less and sleeping more, and her diminished functional ability left her feeling depressed.
The patient made multiple visits to her physician’s office and to the emergency department of various local hospitals for evaluation of her abdominal pain, but no abnormalities were found on laboratory or imaging studies during any of these visits. Abdominal computed tomography (CT) scanning, comprehensive metabolic panels, and complete blood counts were all within normal limits. Physical and abdominal examinations were unremarkable, except for her weight loss. During a visit to a gastroenterologist, an esophagogastroduod-enoscopy and a colonoscopy were performed, but neither produced significant findings.
Four months after her symptoms began, the gastroenterologist ordered duplex ultrasonography, which revealed possible superior and inferior mesenteric artery occlusion. Shortly thereafter, she underwent angiography, which revealed a definitive diagnosis of superior mesenteric artery stenosis. Although the patient was still independent in her activities of daily living (ADLs) at the time of diagnosis, she had lost more than 30 lb and ceased most physical activities, including swimming. However, within 6 hours of undergoing stenting of the superior mesenteric artery, the patient was eating normally. She resumed swimming and all of her usual activities 3 weeks after the procedure. Clopidogrel therapy was also initiated and she followed up with the vascular surgeon at regular intervals.
Case 2
This case involves an 88-year-old white woman who presented to the hospital after experiencing multiple falls and becoming unable to care for herself. According to the patient and her daughter, she had been experiencing postprandial abdominal pain for several months, which had become so severe that she began skipping meals or eating frequent but smaller meals. “I just don’t eat,” the patient stated.
Her medical history was positive for hypertension, congestive heart failure, coronary artery disease, atrial fibrillation, chronic kidney disease, and a remote history of smoking. She was on pravastatin for her hyperlipidemia. During the physical examination, the patient was anxious and tearful. Before the onset of her symptoms, she weighed 141 lb (body mass index [BMI], 25.8), but had lost 39 lb and appeared cachectic with a BMI of 18.7. Laboratory studies revealed an albumin level of 2.6 g/dL (normal, 3.5-5.0 g/dL) and a prealbumin level of 6.8 mg/dL (normal, 19.5-35.8 mg/dL). She was also weak, unable to sit without moderate assistance, and only able to walk six steps at a time, whereas several months earlier, she had been independent in all of her ADLs and instrumental ADLs.
A mesenteric angiogram showed 90% stenosis at the celiac artery origin and complete proximal occlusion of the superior mesenteric artery. The risks of surgery were discussed with the patient, who said, “I would rather die on the operating table than live like this.” The patient’s daughter agreed that her mother should have the procedure.
Because of the patient’s malnutrition, the vascular surgeons opted to transfer her to a skilled nursing facility for hyperalimentation prior to surgery. One month after admission, while awaiting surgery, she had a stroke. She was admitted to the hospital, where she rapidly declined and subsequently died. Had this case been diagnosed prior to the patient losing 39 lb and becoming frail, she might have been amenable to surgery sooner or to endovascular repair.
Discussion
CMI is relatively uncommon, although its exact incidence is difficult to establish because it often goes undiagnosed. Reports suggest it accounts for 5% of intestinal ischemic events,2 typically occurs in patients aged 60 years or older, and affects two to three times as many women as men.5,7 Obtaining a thorough history is paramount for diagnosing CMI. Atherosclerosis, considered the primary cause of CMI, is present in 95% of patients.3,4 Smoking, peripheral vascular disease, prior vascular surgery, coronary artery disease, hypertension, diabetes mellitus, and hypercholesterolemia increase an individual’s risk of developing CMI (Table).3,4,8,9
Pathophysiology and Symptomatology of CMI
Studies indicate that 6% to 24% of patients undergoing aortography for evaluation of coronary or peripheral arterial disease have mesenteric atherosclerotic disease, but only a small percentage are likely to progress to CMI.10 This is explained by the pathophysiology of CMI, which requires understanding how blood circulates to the mesentery. Three main arteries arise from the aorta: the celiac, which supplies the stomach, proximal duodenum, liver, and spleen; the superior mesenteric, which supplies the distal duodenum, small intestine, and proximal colon; and the inferior mesenteric, which supplies the region from the splenic flexure to the upper portion of the rectum. These three arteries sprout multiple smaller arterial branches, which provide extensive collateral circulation should an artery become blocked. As a result, most patients can tolerate stenosis in one or two of the main arteries.4 Progression to CMI or an acute mesenteric ischemic event are more likely to occur in patients with multivessel involvement.11
The main presenting symptoms of CMI are anorexia/weight loss, postprandial nausea and abdominal pain, and sitophobia (Table).12 Patients may also experience vomiting, diarrhea, constipation, and pain after exercise. Postprandial abdominal pain usually starts 15 to 30 minutes after eating4 and is described as cramping or colicky. It typically resolves within 1 to 2 hours, but it can persist for as long as 4 hours.1,2 The abdominal pain corresponds to the volume of food consumed, rather than its nutritional content; thus, many patients begin eating smaller, more frequent meals that contain less fat and protein and are therefore lighter.13
Intestinal angina, considered a hallmark of CMI,14 is thought to occur secondary to a vascular steal phenomenon. While fasting, the gut receives 20% of cardiac output, which rises to 35% after eating. The increase in gastric circulation once food enters the stomach corresponds with a decrease in blood flow to the intestines. The vasculature’s inability to meet the metabolic demands of the intestines produces ischemic symptoms.2
A physical examination is often remarkable for weight loss, sarcopenia, and possibly an abdominal bruit (Table). Half of patients do not present with these classic symptoms, however, and only report nonspecific abdominal pain15 that, in some cases, seems disproportionate to physical examination findings.11
Studies indicate that CMI is often missing from the differential diagnosis, and symptoms commonly result in a diagnosis of failure to thrive. This may be because the symptoms of CMI are nonspecific, mimicking those associated with other conditions, such as a gastrointestinal malignancy. In some cases, symptoms may be misattributed to a comorbid condition.3 Diagnosis of CMI and intervention occur an average of 15 to 18 months after symptom onset.14
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Diagnostic Modalities
Angiography is considered the gold standard for diagnosing CMI. It provides a high degree of clinical accuracy and offers the possibility of intervention; however, it is an invasive procedure, with an overall complication rate of 1.9% to 2.9%. The literature includes reports of external iliac artery dissection and deep vein thrombosis with angiography.16 Despite these risks, angiography may be the procedure of choice, especially for patients whose symptoms are significant.
Duplex ultrasonography, magnetic resonance angiography (MRA), and CT angiography (CTA) are other modalities used in diagnosing CMI. Color duplex ultrasonography is becoming the first choice for initial screening of the mesenteric vasculature. It has a comparatively low cost compared with angiography and is quick to perform, noninvasive, and portable; it can even be performed at the bedside. Ultrasonography has a reported sensitivity of 92% to 100% and a specificity of 92%, and it allows visualization of the celiac and superior mesenteric arteries in 80% to 90% of patients.1,16 However, results are limited by the operator’s skill and the presence of gas in the bowel.13 Even if ultrasonography reveals stenosis of the mesenteric vasculature and decreased blood flow, CMI remains a clinical diagnosis.
Studies of contrast-enhanced MRA have a sensitivity of 95% and a specificity of 90%; however, the grading of stenosis varies greatly by reviewer, which is a drawback of this modality.17 Additional drawbacks include its cost and the need for the patient to hold his or her breath during the procedure. Like duplex ultrasonography, MRA is not good at imaging the inferior mesenteric artery.
CTA—also known as multidetector row CTA—is becoming more widely available and can render three-
dimensional images of the vasculature. For acute mesenteric ischemia, its sensitivity and specificity are 96% and 94%, respectively18; we are unaware of any study comparing angiography with CTA. Compared with MRA, CTA is easier and quicker to perform and also less costly. CTA is increasingly used to help diagnose CMI, and its ability to depict the superior mesenteric and celiac arteries is comparable to that of ultrasonography and MRA.
Diagnosis of CMI is solely based on the patient’s presentation and findings on imaging studies. While laboratory studies may reveal malnourishment, anemia, hypoalbuminemia, and hypocholesterolemia, these findings are not sensitive nor specific to CMI.12 There has been testing looking at early serologic markers for CMI, such as lactate, lactate dehydrogenase, intestinal fatty acid binding protein, and D-dimer, but none of these have been proven helpful in making the diagnosis.13
Management of CMI
Treatment of CMI has evolved over the past two decades and is recommended for symptomatic patients. Primary interventions include surgery and endovascular therapies (with or without stenting). Surgeons sometimes hesitate to attempt these interventions in frail elderly patients with CMI, but the disease process often causes their frailty. Intervention could modify the disease process and help prevent or reverse frailty in these patients, as shown by the case 1 patient.
Success rates reported with open surgical procedures are as high as 90%, and surgical intervention has been associated with a 5-year survival rate of up to 80%.1,2,12 However, open surgical repair is known to have significant morbidity (5%-30%) and mortality (5%-12%) associated with it.4 Whereas surgery was once considered first-line therapy for CMI, endovascular therapies are becoming more common and now account for more than 70% of interventions performed.14 Outcomes are improving as institutions are becoming practiced in endovascular procedures. Endovascular repair is reported to have an overall high success rate, ranging from 80% to 100%, and a 9% morbidity rate and a 3% mortality rate.4 Studies comparing open versus endovascular procedures for CMI have shown open procedures to have higher mortality rates (15% vs 4%, respectively).19,20
Because surgical treatment is more invasive and associated with longer hospitalizations and higher rates of morbidity and mortality than endovascular repair,19,20 the latter option is considered a more acceptable intervention for frail elders.21-24 Studies suggest that more patients who undergo endovascular repair than surgery are discharged to home versus a nursing facility despite these patients having a greater incidence of frailty than their surgical counterparts.25
Medical management alone should be an option only if surgery or endovascular treatment is deemed too risky. Medical therapy can also be administered in conjunction with endovascular or surgical repair, and typically involves treatments for atherosclerosis (eg, statins) and interventions or lifestyle changes to help patients control hypertension and diabetes and to stop smoking.3
Following stent placement, 4 weeks of dual antiplatelet therapy has become the standard of care to decrease the risk of acute thrombosis, followed by daily aspirin doses of 100 mg to 325 mg thereafter.3 Medications such as warfarin, antiplatelet agents, and antispasmodics may help prevent thrombosis, as well as control and palliate symptoms. These agents have been shown to reduce mortality and recurrence in mesenteric vein thrombosis, and it is hypothesized that they can do the same for mesenteric artery atherosclerosis/stenosis.4 Although nitrate therapy by inducing vasodilation may relieve intestinal angina, it does not affect the disease process.4,6,8
Patient follow-up should occur at routine intervals and include taking the patient’s history (to determine if symptoms have recurred) and conducting a physical examination. All aspects of secondary prevention should be reviewed, including cholesterol levels, blood pressure control, diabetes management, and smoking cessation.3 Several studies also recommend performing routine duplex ultrasonography every 6 to 12 months.3,4
Conclusion
CMI, which frequently goes undiagnosed, should be included in the differential diagnosis for patients with failure to thrive, especially for those who have atherosclerotic disease or risk factors for atherosclerotic disease. Proper diagnosis requires obtaining a complete history and using the appropriate imaging modalities. Although angiography remains the gold standard, duplex ultrasonography, MRA, and CTA—which have varying degrees of sensitivity and specificity—are increasingly being used to aid in diagnosis. Failure to treat symptomatic CMI can have serious consequences for the patient, such as starvation, bowel infarction, sepsis, and death. Treatment goals in frail elderly patients should focus on relieving symptoms, resolving weight loss, and preventing acute mesenteric ischemia.
At the time of presentation, the two patients whose cases we discuss would have been appropriate hospice candidates. Although one patient was successfully treated with endovascular stenting, which resolved her symptoms and significantly restored her quality of life, the other was considered too frail for immediate surgery. While undergoing hyperalimentation, she suffered a stroke and died before surgery could be performed. Had she received a diagnosis of CMI prior to progressing to cachexia, she might have had a better outcome.
The authors report no relevant financial relationships.
Dr. Snyder is a geriatrician and palliative medicine physician, and Dr. Baum is the associate director, Geriatric Fellowship Program, Summa Health System, Akron, OH.
Acknowledgments
The authors thank Kathleen Senger, MD, for providing one of the contrasting cases, and Aileen Jencius, MLIS, for her assistance with manuscript preparation.
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