What Clinical Features Lead to the Diagnosis of Acute Mesenteric Ischemia?
Pearls and Pitfalls
• Mesenteric ischemic presents with nonspecific exam findings in early stages; thus, clinicians must maintain a high vigilance（小心谨慎）.
• In the early stages of acute mesenteric ischemia both symptoms and exam findings are vague and nonspecific thus clinicians must maintain high degree of vigilance for chronicity（慢性） of symptoms and risk factors for thrombi/emboli.
• There are four main types of mesenteric ischemia though early on their clinical features and physical exam findings are very similar.
• Delay to diagnosis leads to greater tissue loss, increased morbidity, and increased mortality. This is an easy diagnosis to miss until it is too late.
• There is no defining symptom or exam finding that clinches（确定） the diagnosis of acute mesenteric ischemia.
• Although this disease primarily affects the elderly, mesenteric venous thrombosis affects young people and can have significant morbidity associated.
In 1926, A.J. Cokkinis described mesenteric ischemia as “the diagnosis is impossible, the prognosis hopeless, and the treatment useless.” Today, acute mesenteric ischemia remains a complex disease process that is both difficult to diagnose and difficult to treat. Acute mesenteric ischemia (AMI) remains a rare diagnosis with an incidence of 10 per 100,000 adults and represents less than 1 in every 1000 hospital admissions. AMI is a surgical emergency; despite advances in diagnostic technology, primarily the development of the multi-slice CT scanner, and new surgical techniques, mortality remains high at 30–90%. Unfortunately AMI shares many clinical features with other etiologies of the acute abdomen, often delaying diagnosis unless there is a high index of suspicion when reviewing history and exam findings. Herein（在此） is a review of the historical and clinical features that can be helpful to increase suspicion for AMI.
What Clinical Features Lead to the Diagnosis of Acute Mesenteric Ischemia?
Classically, the AMI patient is an elderly white female in her 60–70s presenting with abdominal pain out of proportion to exam findings and history of cardiovascular disease. Patients may present with a spectrum of additional symptoms, including nausea, vomiting, and forceful evacuation of bowels（强行排便） that progresses to fever, bloody diarrhea（血性腹泻）, and hemodynamic instability once transmural infarction of the bowel（肠壁梗死） occurs. Classic exam findings include “pain out of proportion to exam,” referring to a lack of reproducible（可重复） localizable abdominal tenderness during palpation, and epigastric bruit【（听诊时所听到的）杂音】. While these exam findings are characteristic of AMI, they are dependent on the degree of bowel infarction and will progress to peritoneal abdominal pain only once transmural infarction has occurred.
In one systematic review by Cudnick et al. (2013) of 1970 patients diagnosed with acute mesenteric ischemia, the prevalence of risk factors and physical exam findings suggestive of AMI was summarized. Atrial fibrillation, a history of abdominal pain, and diffuse abdominal tenderness were frequently reported.
Refining Your Diagnostic Gestalt by Underlying Etiology
There a four common types of AMI that relate to the mechanism of bowel insult and can be differentiated early based on patient history and presenting symptoms (Table 27.1). These primary four mechanisms are arterial embolism, arterial thrombosis, non-occlusive mesenteric ischemia, and mesenteric venous thrombosis. Regardless of mechanism, all typically effect the superior mesenteric artery resulting in gut ischemia. (Table 27.2).
Arterial embolism is the most common pathophysiology resulting in AMI and accounts for 40–50% of cases. It often originates from a cardiac source and the patient may have a past medical history of atrial fibrillation, valvular disorder, recent myocardial ischemia, or any pathology that predisposes（倾向） the patient to mural（壁） thrombosis. One-third of patients have had a preceding arterial occlusive event, and these patients typically do not have a history of chronic mesenteric ischemia. Notably, chronic atrial fibrillation managed with appropriate anticoagulation does not decrease risk of arterial embolic pathophysiology. Patients describe an abrupt onset of abdominal pain with rapid worsening, associated with vomiting and forceful diarrhea. Symptom acuity（敏锐度） is related to a lack of collateral circulation（侧支循环） in the splanchnic vasculature（内脏血管）. Exam will likely reveal diffuse abdominal tenderness and other findings consistent with peritonitis. Survival is approximately 50% when diagnosis is made within 24 h of presentation and sharply declines thereafter.
Arterial thrombosis accounts for 25–30% of AMI cases and is often superimposed（叠加的） on pre-existing severe systemic atherosclerotic disease. In many cases, these patients have been diagnosed with or have symptoms consistent with chronic mesenteric ischemia (up to 73%) preceding their acute presentation. Symptom onset tends to be insidious（隐匿的） as the splanchnic vasculature has had ample time to form collaterals（侧支）. Intestinal injury tends to be more extensive（广泛） and devastating（毁灭性） due to proximal nature of the occlusion. Mortality for arterial thrombosis AMI is greatest with a 90% mortality rate across several studies. Symptoms typically are described as a chronic phase of intermittent abdominal pain, weight loss, and diarrhea, followed by an acute episode of severe abdominal pain associated with diarrhea, hemodynamic instability, or gastrointestinal bleeding. Physical exam findings in arterial thrombotic disease are similar to findings in arterial embolism.
Non-occlusive mesenteric ischemia (NOMI) is an etiology of AMI that is seen primarily in critically ill patients resulting from prolonged visceral arterial vasoconstriction and accounts for 20% of the disease burden. These patients are typically severely ill, intubated, or altered such that they are unable to complain of abdominal pain and their exam is limited. Certain medications, such as digitalis, dopamine, and ergot derivatives, as well as cocaine（洋地黄，多巴胺，麦角碱衍生物，以及可卡因）, have been shown to cause NOMI. Past medical history is the largest clue to this pathology and typically includes diagnoses that predispose the patient to low cardiac output such as congestive heart failure, aortic insufficiency, recent cardiovascular surgery, as well as a history of diffuse severe atherosclerotic disease. NOMI has also been well described in hemodialysis patients; thus, clinicians need to maintain a high suspicion in patients presenting with abdominal pain during or immediately after dialysis. NOMI is similar to the concept of demand ischemia in cardiovascular disease during severe systemic illness or during resuscitative（复苏的） efforts which cause physiologic changes resulting in bowel injury.
The least common cause of AMI is mesenteric venous thrombosis (MVT), accounting for just 5–15% of cases, though mortality remains high at 20–50%. Disease occurs when clot forms in the venous arcades（拱廊） and propagates（传播） to occlude the intramural vessels resulting in hemorrhagic bowel infarction. Ninety percent of patients with MVT have at least one of the following three risk factors: (1) hypercoagulability (e.g., thrombophilia易栓症, oral contraceptive避孕药 use, neoplasm肿瘤), (2) recent abdominal trauma, and/or (3) local inflammation (e.g., pancreatitis, diverticulitis憩室炎, etc.) . Approximately 50% of patients will have a personal or family history of pulmonary or deep venous thromboembolism. While AMI is typically a disease of the elderly, MVT predominantly affects patients between the ages of 20 and 40 years without atherosclerotic disease history. These patients often have subacute or late presentations with vague（模糊） diffuse abdominal pain, anorexia(尤指年轻女子害怕肥胖而引起的)厌食, and diarrhea without preceding prodromal symptoms. On exam, abdominal tenderness frequently localizes to bilateral lower quadrants. Exam findings may also include signs of portal hypertension（门脉高压） (e.g., caput medusa, ascites, and hemorrhoids水母头、腹水和痔疮) if the inciting clot occurred well before symptom presentation.
Regardless of etiology, the final common pathway includes bowel infarction though distribution of clot burden determines extent of intestinal damage. MVT is the least likely to present in extremis given the extent of disease required to cause infarction, though all four pathologies can present with Klass’ classic description of severe abdominal pain, bloody stool, and relatively normal physical exam. History is the key to recognizing AMI as a cause of the patient’s pain and determining the etiology of AMI.
What Is the Most Sensitive and Specific Laboratory Test(s) for the Detection of Acute Mesenteric Ischemia? What Is the Utility of Lactate? Are There Other Laboratory Tests Which Are Helpful in Making the Diagnosis?
Pearls and Pitfalls
• No one laboratory test is sufficient to exclude or confirm the diagnosis of AMI.
• Elevated serum lactate level correlates with mortality and irreversible（不可逆） intestinal ischemia, and may be a marker of late disease, but is not diagnostic.
• D-lactate, D-dimer, I-FAPB, and other novel biomarkers may have a role in the early diagnosis of AMI, but further research is required to assess their role.
Unfortunately, there is no single biomarker that is adequate to diagnose acute mesenteric ischemia (AMI). No test has adequate specificity and sensitivity to give a definitive diagnosis, particularly early in the disease process, when prompt recognition and treatment have the opportunity to affect mortality. However, despite small cohorts and heterogeneity in the literature, there are laboratory tests that are helpful adjuncts（附属物） for diagnosis and new biomarkers that show promise in assisting in the early detection of AMI.
Elevated serum lactate levels are nearly ubiquitous(无处不在的) in confirmed cases of AMI, as is an elevated white blood cell count. Both were elevated in > 90% of patients with AMI. Serum lactate is felt to be, unfortunately, a late marker of disease and correlates with both irreversible transmural bowel ischemia as well as mortality. An initial lactate level > 2 mmol/L and maximum lactate level were both associated with increased risk of death, with an OR 3.4 and 2.2, respectively, in one study. However, when assessed for diagnostic power, lactate was found to have a pooled specificity of 86% and sensitivity of only 40%. Alone, an elevated lactate is insufficient to diagnose AMI and may not detect early disease.
The stereoisomer（立体异构体） D-lactate has been proposed as an earlier indicator of intestinal ischemia, reflecting bacterial translocation（细菌移位） indicative of mucosal ischemia. However, this has not borne out（证实） in pooled data, which demonstrated poor sensitivity and specificity, 71% and 74%, respectively. Additionally, measurement of D-lactate may not be feasible at all institutions. In the future, it may have a role in diagnosis and as a marker to guide management, but currently it is not a viable（可行的） option as an isolated diagnostic tool.
D-dimer has been investigated due to the contribution of thrombosis in the pathophysiology of AMI. Powell et al. found that an elevated D-dimer had an 80% sensitivity and 60% specificity in their cohort. However, pooled data revealed the sensitivity and specificity of D-dimer to be 96% and 40%, respectively. D-dimer also does not have utility in predicting bowel ischemia. A negative D-dimer may be reassuring（令人放心） if suspicion for AMI is very low; however, the D-dimer may not be elevated early in AMI and should not be used to definitively rule out the diagnosis.
Elevations in troponin I (TnI) in AMI patients have been noted. Acosta et al. found that in a review of 55 patients with AMI, 28 also underwent TnI testing. Of those patients, 64% were found to have a positive TnI without concurrent(同时发生的) ECG changes or objective evidence of cardiac ischemia. Patients with acute embolic（栓塞） superior mesenteric artery (SMA) occlusion were more likely to undergo TnI testing, and of these patients, 47% were found to have a positive TnI. The authors suggest that this may reflect global increased oxygen demand in the critically ill patient, as well as the catecholamine surge（儿茶酚胺激增） and associated tachycardia associated with acute SMA occlusion. It is important to note that elevations of TnI have been shown to predict higher mortality in elderly patients. TnI may emerge as an adjunctive laboratory marker in the patient with AMI and if positive may suggest an embolic arterial occlusion to providers, but its utility as a diagnostic tool will require further study.
A number of novel biomarkers have been proposed for the diagnosis of AMI, including intestinal fatty acid-binding protein (I-FABP), cobalt albumin-binding assay (CABA), and α-GST (α-glutathione S-transferase) . Ultimately, I-FABP has emerged with promising results. I-FABP is a marker of intestinal mucosal damage, of which one form is excreted(排泄的) in the urine. This is unique among most intestine-specific biomarkers. Most are cleared through the liver and difficult to detect systemically. In one study, I-FABP had a promising sensitivity of 90% and specificity of 89%, though this was not borne out in pooled data. Treskes et al. found a pooled sensitivity and specificity of 75–79% and 79–91%. These experimental biomarkers, in particular I-FABP, will require further research to elucidate(阐明), and then validate, their role in diagnosing AMI.
While no single laboratory test can diagnose AMI, practitioners must recognize that elevated serum lactate levels are a common but likely late finding in AMI and correlate with poor outcomes as well as mortality. Additionally, D-dimer, TnI, and novel biomarkers may be useful in the early diagnosis of AMI, but their diagnostic applicability is not clear at this time.
What Is the Most Sensitive and Specific Imaging Study for the Detection of Acute Mesenteric Ischemia? Is MDCT the Gold Standard?
Pearls and Pitfalls
• Angiography（血管造影） was the previous gold standard for diagnosis of AMI, allowing immediate therapeutic intervention as well.
• CT angiography (CTA) is fast, accurate, sensitive, and specific for the diagnosis of AMI and should be considered the first-line test for AMI.
• Because of the significant morbidity and mortality associated with AMI, it is important to obtain a CTA, even in patients with renal insufficiency.
Rapid and accurate diagnosis of acute mesenteric ischemia (AMI) is crucial to minimize morbidity and mortality. The gold standard test for diagnosis of acute mesenteric ischemia (AMI) was previously formal angiography. Angiography is an attractive option because it provides the opportunity for diagnosis and immediate treatment of AMI.
Advances in multidetector computed tomography (MDCT) technology have allowed CTA to replace formal angiography as a first-line diagnostic test for AMI. There is a large and growing body of literature that strongly supports CTA as the first-line diagnostic test for AMI. CTA is a rapid, noninvasive, and accurate means of diagnosing AMI and is readily（便利地） available to emergency department (ED) physicians. CTA has been found to have a 96% accuracy rate, with a pooled specificity of 93% and a pooled sensitivity of 96%, as well as excellent negative and positive predictive values. Given the high morbidity and mortality associated with delayed diagnosis of AMI and CTA’s excellent performance in detecting AMI, it is important to perform this test early, regardless of renal insufficiency. CTA is also able to detect irreversible bowel wall ischemia, which is useful in discussion with surgical colleagues.
Notably, the World Society of Emergency Surgery guidelines, published in 2017, made a 1A recommendation that any patient with suspicion for AMI undergoes a CTA as soon as possible. Radiologists use a number of different criteria for diagnosis including evidence of arterial occlusion, bowel wall thickening, bowel dilatation, pneumatosis or portal air, fat stranding, perforation, and organ infarction.
Magnetic resonance angiography (MRA) with intravenous contrast is an alternate diagnostic tool for clinicians when suspicious for acute mesenteric ischemia. MRA is particularly strong when diagnosing proximal arterial occlusions and quantifying stenosis(量化狭窄), though it may overestimate the degree of stenosis. There is also no radiation or iodinated contrast exposure to the patient. However, MRI technology, while increasingly common, is still not ubiquitous（无处不在的） among hospitals. Even if available, the increased time to perform the study confers a potential delay in both diagnosis and treatment of AMI. Furthermore, MRA does not reliably demonstrate bowel necrosis. The American College of Radiology 2018 Appropriateness Criteria continues to recommend CTA over MRA. There may be situations where MRA is preferred: for improved vessel mapping or if CTA is absolutely contraindicated or unavailable and the time delay is not prohibitive（高昂得令人难以承受的）.
Angiography will remain a relevant diagnostic and therapeutic tool in the management of AMI in specific patient populations. MRA is an additional diagnostic modality that should be used only in the appropriate clinical setting if there is a high concern for AMI. CTA is reliable, fast, and accurate, and provides critical information that assists clinicians in the diagnosis and management of AMI. CTA should be considered the first-line test for evaluation of AMI.
What Is the Utility of Clinical Scoring Systems for the Diagnosis/Prognosis of Mesenteric Ischemia?
Pearls and Pitfalls
• No validated scoring system exists for the diagnosis of AMI.
• Mortality has been correlated with a number of factors in patients with AMI.
• Delay in diagnosis of AMI > 24 h from onset of symptoms increased risk of mortality by 30% in one study.
• Elevated lactate, elevated shock index, and other indicators of decompensated illness correlate with mortality in AMI, which approaches 100% in severe illness.
There is no widely accepted diagnostic scoring system that has been validated for the diagnosis of acute mesenteric ischemia (AMI). However, a number of historical, exam, and laboratory values when interpreted in aggregate（合计） are suggestive of the diagnosis as well as the prognosis.
Wang et al. are among the first to propose a diagnostic scoring system for AMI. Their model was built from a retrospective review of 106 patients, 42.5% of whom had confirmed mesenteric ischemia. Their scoring system awards points for leukocytosis, increased red cell distribution width, increased mean platelet volume, and elevated D-dimer(白细胞增多、红细胞分布宽度增加、平均血小板体积增加和D-二聚体升高), which when applied to their patient population had a sensitivity of 97.8%, specificity of 91.8%, positive predictive value of 91.8%, and negative predictive value of 98.2%. However, in a letter to the editor, Safiri and Ayubi appropriately raise concerns with Wang’s methodology（方法论）, including comments regarding their very wide confidence intervals, for example, an elevated white blood cell count had a 95% confidence interval of 1.10–235.34; other variables had similarly wide confidence intervals that ultimately may not be clinically meaningful. This likely reflects limitations from a small data pool and implies（意味着） potentially biased data. Additionally, this model has yet to be prospectively validated（尚未得到前瞻性的验证）. At this time, it is difficult to argue for the implementation（执行） of Wang’s model in its current form. However, Wang’s model may form an important starting point upon which other diagnostic tools can be built.
Cudnik et al. in a 2013 meta-analysis of current literature on AMI, eloquently（雄辩地） describe the limitations in current literature. Studies are frequently small, retrospective, and lack adequate control populations to account for intrinsic bias（解释内在偏倚）. Further study is required to articulate（表达） the most appropriate diagnostic model and validate it for clinical practice.
Certain clinical data has been well correlated with an increased mortality in AMI. These include elevated serum lactate levels, delay in diagnosis >24 h from onset of symptoms, associated sepsis, and the presence of bowel necrosis. Symptoms >24 h prior to diagnosis in particular were noted to decrease survival 30% in one study. Regarding risk factors, a number of vascular comorbidities, as expected, have been investigated, but only atrial fibrillation appears to be negatively correlated with mortality in one large study by Bhardari et al. They found that prior diagnosis of atrial fibrillation was independently correlated with increased mortality (p < 0.001), but anticoagulation（抗凝） at time of diagnosis correlated with fewer complications in patients who lived.
A few investigators have attempted to link physiologic data to prognosis. One team looked at the systemic organ failure assessment (SOFA) compared to the multiorgan dysfunction (MOD) score in ICU patients with AMI and found that higher scores, or greater than 13, were associated with 100% mortality in both groups and there was no significant difference between the two scores in terms of predicting outcome. Haga et al. examined a cohort of 110 patients and found that shock index >0.7 and EKG abnormalities, i.e., atrial fibrillation or interval abnormalities, were acceptable approximations of mortality in this cohort. Elevated shock index had an impressive(令人印象深刻的) odds ratio of 11 (p = 0.019), while EKG abnormalities had an odds ratio of 1.7 (p = 0.0022).
While not yet generalizable(可归纳的) or validated, the data suggest that indicators of poor systemic function, such as elevated lactate, sepsis, elevated shock index, elevated SOFA, delay in diagnosis, and comorbidities such as atrial fibrillation all negatively impact mortality in patients with AMI. Further research is required to build models that can assist with diagnosis and prognostication(预测) in these patients who carry such a high risk of mortality already.