Chapter 86. Mesenteric Ischemia

• Acute mesenteric ischemia is a relatively rare clinical entity, but when diagnosis is delayed, it is almost always fatal; therefore, a high index of suspicion is required, especially in those at high risk: the elderly, those with cardiac dysfunction, patients with diffuse atherosclerosis, and those following aortic and cardiac surgery or arterial catheterization.
• The etiology of acute mesenteric ischemia may be embolic, thrombotic, primary vasoconstrictive, or secondary to venous thrombosis. Chronic ischemia is usually due to flow-limiting lesions (stenoses or occlusions) in the presence of inadequate collateralization.
• Classic symptoms of acute intestinal ischemia are central abdominal pain (often out of proportion to the benign abdominal examination), weight loss (an important clue even in the acute presentation), bowel emptying, and altered bowel function (vomiting, bloating, constipation, or diarrhea). Once signs of peritonitis or bloody diarrhea present, shock, sepsis, and death almost always follow.
• Mesenteric angiography is the investigation of choice, offering diagnostic and therapeutic options, whereas computed tomographic (CT) angiogram and duplex ultrasonography may not be definitive. Frequently, the diagnosis is confirmed only at laparotomy.
• Treatment is surgical, with restoration of flow by bypass or embolectomy, resection of nonviable intestine, and liberal use of “second look" laparotomy.

Acute mesenteric ischemia is a relatively rare but often fatal clinical entity. Although little data exist on its true incidence, data from the Swedish Vascular Registry suggest that it may account for just 1 percent of reconstructions for acute thromboembolism.1 Contemporary series, however, continue to report a mortality rate of between 32% and 48%.2,3 Although autopsy studies suggest that atherosclerosis affecting the mesenteric arteries is common (6% to 10%),4 symptomatic mesenteric occlusive disease is rare. However, of patients presenting with acute mesenteric ischemia, one large series found that 43% had prior symptoms of chronic mesenteric ischemia.5 The spectrum of mesenteric ischemia includes occlusive disease secondary to atherosclerotic occlusion with thrombosis, embolism, mesenteric venous thrombosis, and nonocclusive mesenteric ischemia due to vasospasm (Table 86-1). At its most florid, it may present with mesenteric infarction, intestinal perforation, and septic circulatory collapse. This relatively rare but often fatal clinical entity must be considered early in the differential diagnosis of any patient with abdominal symptoms or signs but especially those with a history of intestinal angina, peripheral vascular disease, cardiac dysfunction, aortic surgery or recent aortic catherization, hypotension, or prothrombotic state. Noninvasive tests lack specificity and sensitivity, which indicates that the diagnosis often requires a high index of suspicion, supplemented by a liberal use of diagnostic arteriography (or computed tomographis angiogram) when uncertainty remains. Where doubt exists in the presence of emerging acute abdominal signs or clinical deterioration, diagnostic laparotomy is indicated. This discussion will focus on the etiology, pathophysiology, diagnosis, and management of acute mesenteric ischemia.

The mesenteric circulation is supplied in series by the three major midline branches of the abdominal aorta, namely, the celiac artery, supplying the foregut, hepatic, and splenic beds; the superior mesenteric artery (SMA), supplying the midgut; and the inferior mesenteric artery (IMA) and the internal iliac arteries, supplying the hindgut. An extensive network of actual or potential sites of collateralization exists between individual branch territories and their neighbors, as well as the systemic circulation. The celiac territory may gain supply proximally across the diaphragm from the phrenic and esophageal vessels (that arise from the aorta) and distally from the SMA via the gastroduodenal artery, including the superior and inferior gastroduodenal arteries. The SMA territory may be perfused from the celiac artery, as mentioned, or from the IMA territory via the arch of Riolan, a collateral that runs in the midmesentery and is fed via the ascending branch of the left colic artery (Fig. 86-1). The IMA territory may collateralize proximally, as described, or distally via the inferior hemorrhoidal arteries from the internal iliac artery. Blood from the pelvis may collateralize to the SMA or above from the communications between the sigmoidal-hemorrhoidal vessels to the marginal artery of Drummond (a collateral that runs within 1 to 2 cm of the mesenteric edge of the bowel) and via the arch of Riolan. Vessel caliber decreases progressively from the main aortic branch to the mesenteric vascular arcades distally, ending with an extensive communicating submucosal vascular plexus. This collateral network explains why many individuals may tolerate chronic occlusion of one or two mesenteric vessels without symptoms, but it also explains why acute-on-chronic occlusion of one branch may lead to a catastrophic loss of intestinal perfusion.

The mesenteric circulation receives approximately 20% to 30% of the cardiac output at rest, which may increase by up to 50% after meals.6 As such, the mesenteric circulation receives approximately three times more blood per unit weight than most other body tissues. This blood flow is partly to satisfy the absorptive function of the intestine and perfuse the liver via the portal vein, but it also represents a reservoir function from which blood can be mobilized to other sites (vital organs) at times of stress or increased demand. This preferential shunting of blood to vital organs, if acute or severe, can “sacrifice” the mesenteric circulation, leading to low-flow and ischemic injury. The more metabolically active mucosal layer receives 70% of blood flow, only 30% supplying the muscularis and serosal layers, placing the intestinal mucosa at greatest risk from ischemic injury.6 Within the intestinal villus, passive exchange of oxygen typically occurs between the afferent arteriole and efferent venule, effectively bypassing the capillary network at the villus tip, a phenomenon called oxygen countercurrent exchange. In health, high partial pressures of oxygen ensure that the metabolic needs of the villus mucosa are met despite this shunting, but in deoxygenated states this shunting adversely affects oxygen delivery to the mucosal tip, making it most vulnerable to ischemic injury. A number of extrinsic and intrinsic factors regulate the mesenteric blood flow, leading to a complex interaction between neural, hormonal, and paracrine effectors that regulate the vascular smooth muscle tone in the mesenteric bed and control local blood flow. Vasoactive mediators alter the vascular smooth muscle (VSM) tone of multiple small afferent arterioles, collectively known as resistance vessels, changing their cross-sectional area and blood flow (Table 86-2). The interaction between extracellular agonist (first messenger) and VSM receptor leads to accumulation of intracellular second messengers, such as cyclic adenosine monophosphate (cAMP), Ca2+, and cyclic guanosine monophosphate (cGMP). These second messengers directly or indirectly alter the cytosolic concentration of Ca2+ and dictate whether VSM contracts.7 A functioning cardiovascular system is essential because the mesenteric circulation is often sacrificed to maintain blood flow to vital organs at times of detrimental alterations in cardiac output, blood volume, or arterial blood pressure. Increased sympathetic nervous activity associated with cardiogenic, septic, or hypovolemic shock can further compound flow-related ischemia by inducing intense vasocontriction within the mesenteric bed. High-volume hemorrhage (>35% of blood volume) leads to disproportionate visceral vasoconstriction compared with the reduction in cardiac output.8 When activated postganglionic sympathetic nerves fibers release norepinephrine, stimulating α2-adrenergic receptors on VSM of precapillary arterioles (which are the resistance vessels), this results in vasoconstriction and reduced intestinal blood flow. Some compensation is provided by the simultaneous stimulation of vasodilatory β2-adrenergic receptors on VSM by norepinephrine.9 However the net effect is a rapid reduction in flow followed by a gradual return to prestimulation blood flow levels, a phenomenon known as autoregulatory escape. Exogenously administered norepinephrine similarly can cause nonocclusive mesenteric ischemia (NOMI). Parasympathetic nerves induce vasodilation due to the effect of specific neurotransmitters acetylcholine (ACh, increases cGMP and NO), vasoactive intestinal protein (VIP, increases cAMP), and adenosine triphosphate (ATP). Primary sensory nerves also play a role because their activity through C fibers can inhibit sympathetic impulse flow through the spinal cord or sympathetic ganglia. Indeed, direct antidromic vasodilation can occur as C fibers release neuropeptides, including substance P, calcitonin gene–related peptide, and VIP, in response to luminal signals. Humoral (endocrine) messengers also can affect the mesenteric blood flow, most notably adrenal catecholamines in states of systemic stress, shock, or secreting tumor (pheochromocytoma). Similarly vasocontrictive effects are seen with renal-derived angiotensin II in congestive heart failure and pituitary-derived vasopressin in shock, respectively. Ingested meals and gastrointestinal luminal peptides stimulate a postprandial increase in mesenteric blood flow. This vasodilatory response is regulated, in part, by the increased metabolic activity in the tissues, leading to local accumulation of vasoactive metabolites such as amines, peptides, prostanoids, and adenosine in the presence of a reduced oxygen concentration. Adenosine itself, increasing as a result of energy-dependent processes, may vasodilate in a paracrine fashion. A number of hormones are also released in response to luminal contents, including gastrin, cholecystokinin, and secretin, with net vasodilatory effects.10 Somatostatin, released by the mucosal D cells, induces mucosal vasoconstriction, and synthetic analogs (e.g., octreotide) can induce ischemia.

The unique arrangement whereby the mesenteric blood flow continues in series via the portal vein, supplying much of the metabolic need of the liver, means that oxygen extraction by intestinal tissue remains low at rest. Therefore, intestinal tissues may respond to reduced flow by increasing oxygen extraction from the blood without a requirement for increased blood flow, but this deprives the liver of some of its portal-derived oxygenation, resulting in hepatic ischemia. On a biochemical and microscopic level, acute ischemia of the intestine is characterized by depletion of cellular adenosine triphosphate (ATP), failure of energy-dependent processes (in particular membrane ATPase pumps), cellular swelling, membrane disruption, metabolic arrest, and cell death.11 Hypoxic conditions themselves favor the conversion of the abundant amounts of xanthine dehydrogenase to xanthine oxidase. Accumulating adenosine is metabolized further to inosine and then hypoxanthine but no further without oxygen. With the reintroduction of oxygen on reperfusion, xanthine oxidase converts hypoxanthine to xanthine, producing superoxide (reperfusion tissue injury12). Oxygen free-radicals (OFRs), including superoxide anions (O2−), hydrogen peroxide (H2O2), and hydroxyl radicals (OH−), arise as by-products of the xanthine–xanthine oxidase system, the mitochondrial electron transport system, and the NADPH oxidase system of infiltrating neutrophils. Endogenous defenses against oxidative injury, including intracellular enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and vitamins (C and E), are overwhelmed by the production of OFRs. The OFRs directly attack cell membranes, inducing lipid peroxidation and synthesis of lipid mediators (thromboxane A2, leukotiene B4) and chemotactic peptides (complement component C5a), which promote neutrophil activation and chemotaxis. Sequestration of circulating neutrophils in the microvessels of the intestine begins with constitutively expressed neutrophil L-selectin receptors binding to the postcapillary venule endothelial P-selectin and E-selectin receptors.13 This is the first phase of neutrophil adhesion, manifested by neutrophil rolling along the venular luminal surface. The second phase of neutrophil adhesion occurs after upregulation of the CD11/CD18 integrins and shedding of L-selectin from the neutrophil surface, caused by release of proinflammatory cytokines, platelet-activating factor (PAF), and eicosanoids from the damaged endothelial cell. This halts neutrophil rolling by providing strong neutrophil–endothelial cell adhesion through the interaction of the CD11b/CD18 integrin with the endothelial receptor, intercellular adhesion molecule 1 (ICAM-1).14 Finally, neutrophils transmigrate in response to chemotactic stimuli (such as interleukin-8) and binding by platelet–endothelial cell adhesion molecule 1 (PECAM-1). Neutrophils further damage tissue by releasing superoxide anions via the NADPH oxidase system, secreting myeloperoxidase that catalyzes the production of hypochlorous acid (HOCL), and releasing granular enzymes, including elastase, collagenase, and cathepsin G. Many capillaries fail to perfuse on reinstitution of blood flow, the no-reflow phenomenon, due to loss of local autoregulation combined with mechanical obstruction of narrowed capillaries by enlarged adherent neutrophils.15 This results in incomplete and patchy tissue reperfusion, prolonging hypoxia and exposure of the tissues to toxic metabolites. On a microscopic level, complete ischemia causes detectable injury to the superficial part of the mucosa (the villi) within 20 minutes. As the duration of ischemia increases, the villus loss can be complete before the muscular layers are damaged. Patchy cellular necrosis can extend to mucosal sloughing seen clinically as bloody diarrhea. Ultimately, there is transmural infarction, perforation, and septic peritonitis. Prior to reperfusion, metabolic products such as lactate and other acids are not absorbed via the neglible portal circulation but only through the peritoneal surfaces, accounting for the lack of acidosis commonly observed in patients with acute mesenteric ischemia.

On reperfusion of the acutely ischemic intestine, local injury can induce a systemic phenomenon as metabolic by-products of the ischemic process (lactate, H+, K+, oxygen reactive species, arachidonic acid derivatives, cytokines, possibly endotoxin, and activated leukocytes) are flushed into the systemic circulation. A systemic inflammatory response syndrome (SIRS) is initiated, triggering the complement and coagulation cascades, elaborating cytokines, and provoking widespread endothelial dysfunction and vital organ injury. Even in those surviving this initial phase of acute gut-derived inflammation, the reperfused but injured intestine can continue to be detrimental to the host. The gastrointestinal tract normally is inhabited by a large collection of gram-negative bacteria. Gut-mucosal barrier disruption after ischemia-reperfusion injury allows translocation of these bacteria.16,17 The vast hepatic sinusoid network, lined with fixed-tissue macrophages (Kupffer cells), is strategically located to interact with gut-derived endotoxin and contribute to multiple-organ-system failure (MOSF). Noncardiogenic pulmonary edema is well recognized after intestinal ischemia-reperfusion injury.14,18 Postoperatively, renal and hepatic dysfunction also are common.

A number of factors influence the development of and survival from acute mesenteric ischemia. Factors predisposing to occlusive mesenteric ischemia include hypertension, tobacco use, family history of cardiovascular disease, peripheral vascular disease, coronary artery disease, diabetes, congestive heart failure, prior myocardial infarction, cerebrovascular disease, hypercholesterolemia, and atrial fibrillation.19,20 Nonocclusive mesenteric ischemia results from splanchnic vasoconstriction in response to systemic factors and is associated with acute cardiac dysfunction (myocardial infarction, arrhythmia, left ventricular dysfunction), hypovolemia, and pharmacotherapy.21 Factors predictive of mortality secondary to intestinal ischemia include advanced age, generally poor health, diagnostic delay, and nonocclusive mesenteric ischemia.5 Most patients with asymptomatic high-grade stenosis or occlusions of all three mesenteric trunks will develop symptoms or die during follow-up.22 Therefore, elective revascularization should be considered if they are fit for surgery.

The classic diagnostic triad for chronic intestinal ischemia includes weight loss, abdominal angina, and altered bowel habit.4 The acute presentation may be on a background of chronic intestinal angina or de novo in a previously unsuspected individual with symptoms ranging from subtle signs of intraabdominal sepsis to the dramatic acute abdomen.

Acute Embolic Obstruction

Acute embolic obstruction of the SMA is characterized by acute onset of severe central abdominal pain, often associated with nausea, vomiting, and even diarrhea or a bowel movement. Pain often is described as out of proportion to objective findings and is poorly localized until advanced signs of peritonitis ensue. The patient often adopts a chin-to-knees body habitus, initially restless but later lying quiety once peritonitis develops. In the early stages, abdominal examination may be truly unremarkable, perhaps with some diffuse tenderness without localized peritonitis. Development of an ileus or peritoneal findings is a grave sign suggestive of mesenteric infarction. Bloody diarrhea is a late sign associated with mucosal disruption.20 Initial collapse is not uncommon, but sustained hypotension in the early stages is more likely due to a cardiac than an intestinal cause. Embolic sources, such as arrhythmia (atrial fibrillation), acute myocardial infarction, dilated cardiomyopathy, or a recently instrumented aorta, should be sought.

Acute Thrombotic Occlusion

Thrombotic occlusion occurs often in the setting of chronic symptoms of mesenteric ischemia. When possible, a history of weight loss, intestinal angina, or altered bowel habit should be sought. The presence of chronically developed collaterals may protect against distal ischemia, making the presentation subtle and gradual, with only vague abdominal pain and altered bowel habit initially. However, preexisting atherosclerotic disease in the other major mesenteric trunks will predispose to acute-on-chronic thrombosis of the remaining trunk, critically restricting flow to the entire mesenteric bed and leading to massive mesenteric infarction.

Nonocclusive Mesenteric Ischemia

There is increasing awareness of nonocclusive mesenteric ischemia (NOMI). Any systemic hypoperfusion state can threaten the mesenteric territory, with local vasoconstriction leading to a severely reduced mesenteric perfusion. Mesenteric vasoconstriction may be precipitated by a variety of shock states, namely, cardiogenic, septic, hypovolemic, and even anaphylaxis.23 Furthermore, drugs commonly used to treat acute cardiac dysfunction (digoxin, β blockers) and those employed to support the failing circulation (catecholamines, vasopressin) may exacerbate mesenteric vasoconstriction. Therefore, NOMI should be considered early in any hypotensive patient with suggestive findings.21 Clinical signs are often vague, with new or persistent ileus, abdominal distention, or sepsis of unknown source. Rectal mucus, melena, or frank blood are nonspecific but may point to bowel ischemia. There may be a role for gastrointestinal balloon tonometry in indentifying patients with or at risk of developing NOMI. Recreational drugs (e.g., cocaine) have been reported recently to cause acute NOMI, and a history should be sought if suspicion arises.24

Mesenteric Vein Thrombosis

Mesenteric vein thrombosis most often results in a delayed presentation, often preceded by several weeks of intermittent abdominal pain and altered bowel habit,2 but it also can cause acute abdominal signs and fever. It should be suspected in patients with previous abdominal surgery, thrombophilia, prior mesenteric or deep venous thrombosis, cirrhosis, or malignancy.

Miscellaneous Causes of Acute Mesenteric Ischemia

Other pathologic processes occasionally causing acute mesenteric ischemia include aortic surgery (when the IMA is ligated and collateral flow is insufficient25), aortic dissection26 (even when mesenteric vessels are not directly involved, hypotension may combine with pseudocoarctation to provoke ischemia), aortic trauma, mesenteric aneurysm rupture, arteritis, fibromuscular dysplasia (FMD), and extrinsic mechanical vascular obstruction. Acute intestinal ischemia also may arise as a result of extrinsic mechanical compression of the arterial inflow or venous outflow. As low-pressure conduits, veins are most susceptible to extrinsic compression; intramural venous plexi may be obstructed due to wall distention, whereas mesenteric veins may be compressed by tumor, adhesion, volvulus, hernia, or intussusception.

The single most important factor is clinical suspicion followed by investigation. A delay in diagnosis may be lethal.20 No single blood marker has proved to be an adequate screening test. Lactic acidosis has poor sensitivity in detecting bowel ischemia. Despite advances with noninvasive radiologic testing, mesenteric angiography remains the definitive test. ACT angiogram may yield similar information while also demonstrating abnormalities of the bowel wall. Even with high-quality imaging studies, laparotomy may be required for definitive diagnosis. A suggested algorithm for the initial approach to a patient with suspected acute mesenteric ischemia is given in Fig. 86-2.

Laboratory Serum Parameters

No serum marker has been proven to be sensitive and/or specific enough to confirm reliably the presence or absence of acute mesenteric ischemia. Nevertheless, some are clinically useful. In acute mesenteric ischemia, a leukocytosis is almost invariably present, except in those who are immunocompromised owing to comorbid disease, advanced age, corticosteroid treatment, or profound critical illness. A neutrophilia is typical (total white blood cell typically = 16,000 to 30,000/μL), and early white cell forms are common. Platelets typically are reduced. Coagulopathy may be present in advanced mesenteric ischemia with sepsis or perforation. Arterial blood gases frequently are normal initially, but in the later stages, metabolic acidosis and acute hypoxia may supervene. Lactic acidosis is often a late finding. Prerenal azotemia is a grave indicator, signaling hypovolemia, sepsis, nephrotoxic effect, or disseminated intravascular coagulation (DIC). The erythrocyte sedimentation rate (ESR) and later C-reactive protein (CRP) level may rise. Potential alternative serum markers, such as creatinine kinase (CK) BB isoenzyme, lactate dehydrogenase, intestinal isoenzyme of alkaline phosphatase, diamine oxidase, hexosaminidase, and aspartate transferase, have not proved sufficiently sensitive or specific. The most encouraging markers are serum inorganic phosphate,27 α-glutathione-S-transferase,28 and d-lactate.29 Another possible marker is intestinal fatty acid–binding protein (I-FABP), which is currently the focus of a prospective trial.

Plain Abdominal Radiogram

Plain abdominal radiographs may reveal supporting information such as heavy calcification of the abdominal vasculature, although this is neither sensitive nor specific. In a retrospective series of 23 patients with acute mesenteric ischemia, 26% had normal plain films. Nonspecific signs of ischemia, such as intestinal dilation or gasless abdomen, may be present, but the greatest value of the abdominal radiograph is in establishing an alternative diagnosis. In the advanced stages of mesenteric ischemia, mural changes such as wall thickening or valvulae conniventes, “thumb printing,” or intramural gas (pneumatosis intestinalis) may be present.30 Intrahepatic portal vein pneumatosis or free intraperitoneal gas also may be seen.

Ultrasound

B-mode ultrasonography is quick, readily available, noninvasive, and well tolerated by most patients with abdominal pain. When acute mesenteric ischemia is present, ultrasonography may reveal a thickened (>5 mm) bowel wall and signs of ileus (distended bowel loops and hypoperistalsis). In advanced cases (mesenteric infarction), ultrasound may show intraperitoneal fluid, pneumatosis, or intrahepatic portal venous gas. However, ultrasonography is operator-dependent and may be confounded by the degree of intraluminal intestinal gas or by obesity. For patients with suspected chronic mesenteric ischemia, duplex ultrasonography has become the investigation of choice by many. A peak systolic velocity of greater than 275 cm/s in the SMA or greater than 200 cm/s in the celiac artery or no flow signal (in the SMA or celiac artery) predicts a stenosis of greater than 70% with a sensitivity of 89% and aspecificity of 92%.31

CT Scan and CT-Angiogram

CT scanning is the radiologic investigation of choice for acute abdominal pain at many centers. Oral contrast enhancement may give better luminal definition but is not used by many centers, especially in the emergency situation. Intravenous contrast enhancement (CT-angiography, CTA) further elaborates the major vessel flow and tissue perfusion (Fig. 86-3). All three mesenteric vessels can be identified and patency assessed by their contrast content. Alternatives to iodinated contrast agents, such as gadolinium, may be used for patients with a contraindication to standard contrast material. Ischemic bowel wall typically is seen as thin and poorly enhanced, more prominent on the antimesenteric border in NOMI. Air may be seen in the bowel wall or the portal vein. Reperfused bowel segments appear enlarged and edematous, often with increased mucosal and submucosal enhancement due to interstitial extravasation of contrast material.32 With the increased availability of modern multislice helical CT scanners, rapidly acquired high-quality CTA images of the main mesenteric trunks and small collaterals are possible.64 Compared with mesenteric angiography, CTA may prove safer, cheaper, and better tolerated and result in decreased radiation exposure for both patient and staff.

MRI and Mr-Angiography (Mra)

The superior soft-tissue definition and non-contrast-enhanced angiographic ability of MRI give it potential advantages in patients with an acute abdomen.33 Recent advances in MRA technology and the use of contrast-enhanced (CE) techniques have shortened acquisition times and reduced the impact of motion artifacts, which previously had restricted its use.34 MRA may prove to be the investigation of choice in chronic mesenteric ischemia, where it has been suggested that CE-MRA is superior to digital subtraction angiography for simultaneous exploration of the abdominal aorta and its major branches, and it can be coupled with measurements of flow and assessment of surrounding soft tissues.35 However, at present, its use in emergency practice remains experimental.

Angiography

Mesenteric angiography remains the most specific test for the diagnosis of mesenteric ischemia, giving objective, reproducible evidence and in some instances providing therapeutic catheter-based options.36 Not only does it identify the location of the flow-limiting lesion, but it also may give information about distal runoff and the extent of collateralization, allowing the most appropriate therapy to be planned. However, it cannot discern whether or not intestinal infarction has occurred, and therefore, treatment always must be planned with full assessment of clinical and laboratory parameters, especially if a catheter-based therapy is planned.37

Thrombotic occlusion usually occurs on a background of chronic atherosclerotic disease, where lesions tend to be at or near the ostium, producing an abrupt cutoff of contrast (Fig. 86-4). The chronicity of the atherosclerotic process may be indicated by the presence of multivessel disease or the presence of large collaterals refilling the branch territories distally. One must consider the clinical findings carefully because chronic mesenteric occlusions are seen in up to 60% of the octogenarian population but cause symptoms in only 5%.

Mesenteric artery emboli present as sharp, rounded filling defects with a typical meniscus sign. Distal vessels may refill through collateral vessels. Emboli typically lodge at the sites of vessel narrowing, such as the origin or a bifurcation. The SMA is affected most often because it is a relatively large vessel with high flow, and its orientation encourages antegrade entry of the embolus. SMA emboli typically occlude the vessel just distal to the middle colic artery origin.

Nonocclusive mesenteric ischemia is typified by diffuse narrowing of the mesenteric artery and its branches, alternating areas of narrowing and dilation of the main trunk and branches (“string of sausages sign”), spasm of the peripheral vascular arcades, impaired filling of intramural vessels, and slow flow with increased reflux of contrast material into the aorta during selective injection. An increase in vessel caliber after transcatheter papaverine injection may clinch the diagnosis. Mesenteric venous thrombosis is seen on the later phase of angiography with contrast stasis and lack of portal venous phase filling.

Initial management includes identifying and correcting immediately any life-threatening hypoperfusion or electrolyte abnormalities while planning further definitive steps toward diagnosis and treatment. Simple airway management with supplemental oxygen by mask, titrated to achieve oxygen saturation above 95%, will suffice in patients who are breathing spontaneously. Obtunded patients typically should be intubated electively, bearing in mind the risk of aspiration owing to gastroparesis and intestinal ileus. A wide-bore nasogastric tube should be placed for intestinal decompression. Acute electrolyte disturbances such as hypokalemia, hypomagnesemia, and hypophosphatemia should be corrected. Broad-spectrum antibiotics (e.g., second-generation penicillin or third-generation cephalosporin, along with anaerobic coverage) should be administered intravenously. Analgesia should not be withheld in the conscious patient. Systemic heparinization is advocated once the diagnosis is strongly suspected, unless there are absolute contraindications. The goal is a partial thromboplastin time (PTT) of greater than 2 times control.

Diagnostic and Therapeutic Selective Mesenteric Angiography

Where there is diagnostic doubt in a patient with suspected mesenteric ischemia but stable clinical assessment, diagnostic mesenteric angiography is advocated.38 Modern catheters and techniques reduce the risks of bleeding, dissection, and embolization. In a well-resuscitated patient, small-volume nonionic contrast and digital subtraction angiography (DSA) limit the risk of nephrotoxicity and contrast reaction. An initial flush aortogram may define the origins of the major vessels and outline possible collateral pathways. Selective mesenteric artery catheterization allows for thorough assessment of individual arterial territories and opens up therapeutic options.39

For NOMI, catheter-based therapy is the treatment of choice in the absence of definitive signs of intestinal infarction.40 Papaverine (30 to 60 mg/h) is infused selectively into the SMA for a period of 24 hours. Repeat flush angiography should confirm partial or complete resolution of spasm 30 minutes after beginning the infusion and prior to the patient's return to the ICU. Papaverine is a potent phosphodiesterase inhibitor, leading to increased intracellular cAMP and vasodilation.41 Because of extensive hepatic first-pass metabolism, systemic effects such as hypotension generally are modest. Failure of therapy may be signaled by cardiovascular instability, progression of clinical symptoms or signs, and catheter displacement or blockage.

Occlusive mesenteric ischemia traditionally requires surgery. However, increasing numbers of interventional radiologists are exploring the use of catheter-based therapies as long as there is no frank intestinal infarction. A number of techniques are available for recanalization, including suction clot retrieval, thrombolysis, angioplasty,42 and stenting.43 All these techniques remain investigational and should be conducted only in collaboration with an appropriately trained surgeon and an interventional radiologist and with appropriate monitoring and reassessment of the patient.44 Even when a decision is made to proceed to surgery, continued infusion of papaverine or heparin into the occluded vessel may improve distal circulation and prevent clot propagation pending definitive surgery.

Minimally Invasive Surgery

In the setting of high suspicion of acute mesenteric ischemia, some have advocated laparoscopic assessment of the abdominal contents45 and have suggested that this can be done safely with high diagnostic accuracy.46 The minilaparoscopy is being advocated increasingly in the critical care setting where there remains diagnostic doubt in a deteriorating patient, and some have done this safely at the bedside.47 The generally poor results of open surgery, even in good hands, have encouraged some surgeons to explore less invasive alternatives using laparoscopic techniques. Some practitioners have claimed improved survival and reduced morbidity using this approach, but whether these results in specialized centers can be extended to other settings is unknown.48

Open Surgery

Often the definitive assessment and management of acute mesenteric ischemia require open surgery.49 The surgeon should repeat the abdominal examination once the patient is anesthetized. In the absence of muscle tone and tenderness, new pathology, such as an abdominal mass or aortic aneurysm, may be detected. Adequate exposure generally requires a full midline laparotomy with transperitoneal approach. Although retroperitoneal approaches to the aorta and branches are useful in chronic mesenteric revascularization, they do not allow adequate assessment of intestinal perfusion and viability in the acute setting. The initial aim is to confirm the diagnosis and rule out any major confounding disease. The acutely ischemic intestine may appear remarkably normal prior to infarction and before reperfusion. Changes may be focal, segmental, or global depending on the etiology of the ischemia. The intestine is inspected for loss of sheen, discoloration (gray through black), and lack of peristalsis. SMA thrombosis typically occurs at the origin, so the distribution of ischemia classically involves the entire small bowel and proximal half of the colon. SMA embolism, on the other hand, may spare the right colic branch and proximal jejunum branches if it lodges distal to the origin. However, the clot may lodge at the origin, giving a similar pattern to thrombosis. Microemboli typically disperse and lodge distally, creating patchy areas of ischemia with normal intervening segments. Delicate palpation for arterial pulsation must be carried from the root of the SMA to its mesenteric branches. Visible pulsation may be seen in the mesenteric arterial arcades. More objective assessment by means of sterile Doppler ultrasound probe may reveal an absence of flow in the main branches, arcades, or the intestine itself. Previously used assessment with intravenous fluorescein dye and an ultraviolet lamp is now rarely practiced clinically.50

Except in very advanced cases where perforation has occurred or is imminent, revascularization should precede the resection of nonviable bowel. In the presence of frank necrosis, quick segmental resection may be carried out using a gastrointestinal linear stapling device without undue delay of revascularization. On reperfusion, remarkable recovery is often witnessed in seemingly unsalvageable segments, especially important when near-total small bowel resection seems inevitable at first inspection, with the consequent implications of lifelong parenteral nutrition therapy. Caution must be exercised in the setting of an elderly, infirm, or hypotensive patient because the systemic effects of reperfusion of a profoundly ischemic intestine may lead to catastrophic acidosis, hyperkalemia, myocardial depression, and refractory shock. The initial approach to revascularization in most cases is an attempt at embolectomy; if satisfactory antegrade flow cannot be achieved, then one proceeds to mesenteric artery bypass.

Superior Mesenteric Artery Embolectomy

The superior mesenteric artery may be exposed and controlled transperitoneally at the base of the transverse mesocolon, where it courses from its midline aortic origin, obscured by the body of the pancreas in its proximal few centimetres, and then rises over the fourth part of duodenum to give off its first branch, the right colic artery, and enter the mesentery. Its localization by palpation may be assisted by sterile Doppler probe in the bulky mesentery. After splitting the mesentery and retroperitoneum in the line of the vessel, it is controlled with vascular loops at the level of its bifurcation. Only minimal dissection of the numerous small perivascular nerves and lymphatics is required. Standard approach is via a tranverse arteriotomy, but longitudinal opening may help if vessel caliber is small or if bypass is to be expected. Proximal embolectomy is carried out first with a balloon catheter (size 3F or 4F). If pulsatile aortic flow is restored, the vessel is reoccluded, and the surgeon proceeds to distal embolectomy.51 Mesenteric bypass is indicated if there is failure to pass the catheter, inadequate inflow, or a heavily diseased vessel. Distal embolectomy is performed gently manually, guiding the balloon catheter (size 3F) into the major branches, until all thrombus is retrieved and backbleeding is seen. The arterial closure should maintain an adequate lumen and is best achieved with interrupted monofilament sutures, sometimes requiring a patch angioplasty with autologous vein. Restoration of pulsatile flow should be assessed clinically by palpation and visualization of the intestinal perfusion and checked intraoperatively with sterile Doppler probe (at the bowel-intestinal margin) or duplex ultrasound. Spasm is common in the distal vessels and may be relieved by perivascular infusion of papaverine (30 mg).

Superior Mesenteric Artery Bypass

Mesenteric artery revascularization is indicated to restore intestinal blood flow if the diagnosis is mesenteric thrombotic occlusion or adequate inflow is not achieved at embolectomy.1 A number of surgical approaches are available, but in these fragile patients a quick, durable approach is to bring retrograde inflow from the common iliac artery. The choice of inflow vessel is influenced by the quality and patency of the common iliac arteries. Either right or left can provide a suitable graft configuration. Should a vein be chosen secondary to a contaminated field, the left iliac is preferred to avoid potential kinking. If the infrarenal aorta is chosen, a nonocclusive clamp may be used. In the absence of a suitable infrarenal inflow vessel, the supraceliac aorta may be approached through the lesser sac for inflow. The choice of arterial bypass conduit is a matter of debate. Prosthetic material is easy to handle, obviates the need for autologous vein harvest, and reduces operative time. Indeed, even in the presence of moderate contamination, the risks of graft infection remain low when polytetrafluoroethylene (PTFE) or antibiotic-impregnated (rifampin 1 to 60 mg/mL) Dacron is used. In the presence of gross fecal contamination, an autologous vein graft is preferred, the reversed long saphenous vein being most suitable. The inflow anastomosis is classically end to side, and the outflow anastomosis is easiest to construct end to end after division of the superior mesenteric artery or end to side using the anterior arteriotomy employed for thrombectomy.

Intestinal Viability

Clinical assessment by an experienced surgeon remains the most widely practiced method to determine intestinal viability. A sensitivity of 82% and a specificity of 91% were achieved using the following factors: presence of visible pulsation in the mesenteric arcades, bleeding, color, and peristalsis.50 Increasingly, most vascular surgeons now confirm their clinical findings with a sterile Doppler ultrasound flow detector (5 MHz), detecting pulsatile Doppler signals at the mesenteric arcades and intestinal surface. The goal of intestinal resection is to remove areas of nonviable bowel and leave sufficient viable bowel to sustain independent life. In general, if a large segment (>6 ft of small intestine) of obviously viable bowel can be identified, then nonviable segments should be resected liberally. Restoration of continuity is preferred; anastomoses may be hand sewn to preserve more functioning intestine, but a stapler may be quicker. In the presence of gross contamination or doubtful viability, creating a stoma may be considered, but in this setting a “second look” laparotomy (after 18 to 36 hours) would allow adequate resuscitation of the patient and clearer differentiation of bowel viability.52 In the case where a second look is required, obviously necrotic segments may be resected using a linear gastrointestinal stapling device, and continuity need not be restored, cutting operative time. A tunneled central venous catheter should be placed at the time of surgery in most of these patients to facilitate long-term parenteral nutrition.

Postoperative Care and Follow-Up Surveillance

Postoperative care must be in an intensive care setting if acceptable results are to be achieved in these high-risk patients. Second-look laparotomy should be the rule rather than the exception and, when planned at the initial surgery, must be adhered to despite the patient's clinical course.19 Reperfusion of the ischemic intestine leads to inflammatory edema of the affected segments, and this, combined with large volumes of intraluminal fluid sequestration, places these patients at risk for developing abdominal compartment syndrome in the postoperative period53 (see Chap. 42). Beyond basic fluid management and cardiorespiratory support, attention must be given to nutritional support. In the catabolic postoperative recovery phase, demands are increased, often on a background of chronic malnourishment and often compounded by dysfunctional reperfused bowel and short bowel syndromes. After major resections, postoperative parenteral nutrition invariably is required, often for extended periods, because even viable segments often have prolonged absorptive and motility dysfunction for extended periods.54 Postoperative heparin therapy should be continued in the absence of bleeding diathesis, and oral warfarin should be commenced, with a target International Normailzation Ratio (INR) of 2.0 to 3.0, as soon as oral diet is resumed. In the case of embolic disease, a primary source should be sought by transthoracic or transesophageal echocardiography and full aortic (chest and abdomen) CT scanning.65 Thoracic aortic mural thrombus is an infrequent cause of emboli that is being recognized with increasing frequency by transesophegeal echocardiography and confirmed by CT scanning.65 Thrombotic occlusions especially of the mesenteric vein should prompt a thrombophilia evaluation. Secondary prevention strategies such as smoking cessation and dietary and therapeutic lipid control may prevent further cerebrovascular and mesenteric vascular events.

Despite numerous advances in the assessment, diagnosis, and treatment of mesenteric ischemia, the mortality rate remains very high even in specialist centres (Table 86-3). Diagnostic delay is perhaps the greatest hurdle to improvement. Most patients who survive the initial perioperative period regain independent living, with results comparable with elective revascularization of chronic mesenteric ischaemia.55 The sequelae of short-bowel syndrome may necessitate home parenteral feeding for a period in many and for the long term in a third of survivors.54 Our group has highlighted the need for continued surveillance of mesenteric bypass grafts to improve the secondary patency and avoid recurrent ischemia.56