CHAPTER 114 Intestinal Ischemia
Intestinal ischemia produces a broad spectrum of disorders, depending on the onset, duration, and cause of the injury; the area and length of bowel affected; the vessel involved; and the degree of collateral blood flow. Variability in these factors influences not only the presentation of the ischemic event but also its treatment and outcome. Ischemic injury may be acute or chronic. It may be caused by a disturbance in the arterial supply or venous drainage of the bowel and involve the small intestine, the colon, or both.
Since the development and widespread use of colonoscopy, angiography, computed tomography (CT), and other imaging modalities, various types of ischemic injury to the gastrointestinal tract have been recognized and increasingly appreciated (Table 114-1; see also Tables 114-2 and 114-4). Our concepts of their pathogenesis, diagnosis, and management have been so altered since the 1980s that much of what has been written in the past is no longer applicable. In this chapter we describe the spectrum of ischemic damage to the gastrointestinal tract and discuss the management of these conditions in light of recent advances.
|Acute mesenteric ischemia*||25|
|Focal segmental ischemia*||<5|
|Chronic mesenteric ischemia||<5|
The celiac axis (CA), superior mesenteric artery (SMA), and inferior mesenteric artery (IMA) supply almost all of the blood flow to the digestive tract.1 There is marked variability of vascular anatomy among individuals, but typical patterns have emerged from anatomic dissections and abdominal angiographic studies.
The CA (Fig. 114-1) arises from the anterior aorta and typically gives rise to three major branches: the left gastric artery, the common hepatic artery, and the splenic artery. The common hepatic artery gives rise to the gastroduodenal, right gastroepiploic, and anterior superior pancreaticoduodenal arterial branches. The splenic artery gives off pancreatic and left gastroepiploic arterial branches. The CA and its branches supply the stomach, duodenum, pancreas, and liver.
Figure 114-1. Diagram of typical celiac axis (CA) anatomy and its anastomoses with the superior mesenteric artery (SMA). A, aorta; AIPD, anterior inferior pancreaticoduodenal artery; ASPD, anterior superior pancreaticoduodenal artery; CP, caudal pancreatic artery; DP, dorsal pancreatic artery; GD, gastroduodenal artery; H, common hepatic artery; LG, left gastric artery; PIPD, posterior inferior pancreaticoduodenal artery; PM, pancreata magna; RGE, right gastroepiploic artery; S, splenic artery; TP, transverse pancreatic artery.
(From Nebesar RA, Kornblith PL, Pollard JJ, Michels NA. Celiac and superior mesenteric arteries: a correlation of angiograms and dissections. Boston: Little, Brown; 1969.)
The SMA (Fig. 114-2) has its origin from the anterior aorta near the neck of the pancreas. It gives rise to five major vessels: the anterior and posterior inferior pancreaticoduodenal vessels, middle colic, right colic, and ileocolic arteries, as well as to a series of jejunal and ileal branches, all of which supply their named portions of intestine. These intestinal branches typically form a series of arcades, and from the terminal arcade, numerous straight vessels arise that enter the intestinal wall.
Figure 114-2. Diagram of typical superior mesenteric artery (SMA) anatomy. AIPD, anterior inferior pancreaticoduodenal artery; COL, colic branches; IL, ileal branches; IC, ileocolic artery; JEJ, jejunal branches; MC, middle colic artery; PIPD, posterior inferior pancreaticoduodenal artery; RC, right colic artery.
(From Nebesar RA, Kornblith PL, Pollard JJ, Michels NA. Celiac and superior mesenteric arteries: a correlation of angiograms and dissections. Boston: Little, Brown; 1969.)
The IMA (Fig. 114-3) arises 3 to 4 cm above the aortic bifurcation close to the inferior border of the duodenum. It branches into the left colic artery, gives off multiple sigmoid branches, and terminates as the superior rectal artery. The IMA and its branches supply the large intestine from the distal transverse colon to the proximal rectum. The distal rectum is supplied by branches of the internal iliac (hypogastric) artery.
Figure 114-3. Diagram of typical inferior mesenteric artery (IMA) anatomy and its anastomoses with the superior mesenteric artery (SMA). AOR, arc of Riolan; ASC, ascending branch of the left colic artery; CA, central artery; DSC, descending branch of the left colic artery; LMC, left branch of middle colic artery; MA, marginal artery; MC, middle colic artery; RMC, right branch of middle colic artery; S, sigmoid branches; SR, superior rectal artery.
(From Nebesar RA, Kornblith PL, Pollard JJ, Michels NA. Celiac and superior mesenteric arteries: a correlation of angiograms and dissections. Boston: Little, Brown; 1969.)
Abundant collateral circulation to the stomach, duodenum, and rectum accounts for the paucity of ischemic events in these areas. The major anastomosis between the CA and the SMA is formed from the superior pancreaticoduodenal branch of the CA and the inferior pancreaticoduodenal branch of the SMA. These vessels constitute the pancreaticoduodenal arcade and provide blood to the duodenum and the pancreas. The splenic flexure and sigmoid colon have limited anastomoses, and ischemic damage is more common in these locations.
There are three potential paths of communication between the SMA and IMA: the marginal artery of Drummond, which is closest to and parallel with the wall of the intestine; the central anastomotic artery, a larger and more centrally placed vessel; and the arc of Riolan, an artery in the base of the mesentery. In the presence of SMA or IMA occlusion, a large collateral termed the meandering artery may be identified angiographically and represents a dilated central anastomotic artery or arc of Riolan (Fig. 114-4). It is critical to determine the direction of flow within a meandering artery before sacrificing the IMA, such as during aortic aneurysm surgery, lest the IMA be the main vessel supplying blood to the small bowel because of an occluded SMA.
Figure 114-4. Film from a flush aortogram of a patient with superior mesenteric artery (SMA) occlusion. The presence of a prominent meandering artery indicates that the collateral channels have been present for some time and that the occlusion is not acute. The arrows show the direction of flow from the inferior mesenteric artery to the SMA.
(From Boley SJ, Brandt LJ, Veith FJ. Ischemic disorders of the intestines. Curr Probl Surg 1978; 15:29.)
Ischemic injury of the intestine results from deprivation of oxygen and nutrients necessary for cellular integrity. Remarkably, the bowel can tolerate a 75% reduction of mesenteric blood flow and oxygen consumption for 12 hours with no changes on light microscopy, because only one fifth of the mesenteric capillaries is open at any time, and when oxygen delivery is decreased, the bowel adapts by increasing oxygen extraction.2 Below a critical level of blood flow, however, these compensatory mechanisms are overwhelmed and no longer protective.
When a major vessel is occluded, collaterals open immediately in response to the drop in arterial pressure distal to the obstruction and remain open as long as pressure in the vascular bed distal to the obstruction remains below systemic pressure. After several hours of ischemia, however, vasoconstriction develops in the obstructed bed, elevating its pressure and reducing collateral flow. If sustained for a prolonged period, the vasoconstriction can become irreversible and persist even after correction of the cause of the ischemic event. Such persistent vasoconstriction explains the operative findings of progressive bowel ischemia after cardiac function has been optimized and in the absence of arterial or venous obstruction.
Blood flow is affected by a variety of systemic, humoral, local, and neural influences. The sympathetic nervous system, mainly via α-adrenergic receptors, is of primary importance in maintaining resting splanchnic arteriolar tone; other vasoactive substances, including angiotensin II, vasopressin, and prostaglandins, also have been implicated in the pathogenesis of ischemic injury.
Ischemic damage results both from hypoxia during the period of ischemia and reperfusion injury when blood flow is re-established. More reinjury from brief ischemia appears during reperfusion, but as the ischemic period lengthens, hypoxia becomes more detrimental than reperfusion3; the injury after three hours of ischemia and one hour of reperfusion is more severe than that after four hours of ischemia. Reperfusion injury has been attributed to many factors, including reactive oxygen radicals. When molecular oxygen is reduced in univalent steps, superoxide, hydrogen peroxide, and hydroxyl radicals are formed. These oxygen radicals damage an array of molecules found in tissues, including nucleic acids, membrane lipids, enzymes, and receptors; such widespread damage can result in cell lysis, impaired cell function, and necrosis on reperfusion of ischemic tissues.
A potent source of oxygen radicals in ischemic, reperfused tissue is the enzyme xanthine oxidase (XO), the rate-limiting enzyme in nucleic acid degradation. In non-ischemic tissue, this enzyme exists as a dehydrogenase (XDH) that uses nicotinamide adenine dinucleotide (NAD) rather than O2 as the electron acceptor during purine oxidation; as a result, it does not produce oxygen radicals. During ischemia, XDH is converted to XO with production of reactive oxygen radicals. Inhibition of XO by allopurinol dramatically attenuates the epithelial cell necrosis and the increased microvascular permeability seen during reperfusion.
Neutrophils are another source of reactive oxygen metabolites. During reperfusion, XO-derived oxidants initiate the production and release of leukotriene B4 and platelet-activating factor, which lead to neutrophil adherence and migration. The adherent leukocytes mediate microvascular injury by release of proteases and physical disruption of the endothelial barrier. Oxygen radical scavengers (superoxide dismutase, dimethyl sulfoxide), XO inhibitors, and agents that inhibit leukocyte adherence and migration have been shown experimentally to protect various organs against reperfusion injury, but are not yet used clinically because, in large measure, they must be given before or coincident with the ischemic injury to have protective effects.3
Intestinal ischemia can be classified as acute or chronic and of venous or arterial origin. In the acute forms, intestinal viability is threatened, whereas in the chronic forms, blood flow is inadequate to support the functional demands of the intestine. Acute mesenteric ischemia (AMI) is much more common than the chronic type, and arterial disease is more common than venous disease. Arterial forms of AMI include SMA embolus (SMAE), nonocclusive mesenteric ischemia (NOMI), SMA thrombosis (SMAT), and focal segmental ischemia (FSI) (Table 114-2). Acute mesenteric venous thrombosis (MVT) and FSI are the venous forms of AMI.
|Nonocclusive mesenteric ischemia||25|
|Mesenteric venous thrombosis||10|
|Focal segmental ischemia||5|
SMA, superior mesenteric artery.
AMI results from inadequate blood flow to all or part of the small intestine and can involve the right half of the colon because its blood supply is from the SMA. Regardless of the cause of the ischemic insult, the end results are similar: a spectrum of bowel injury that ranges from transient alteration of bowel function to transmural gangrene. Clinical manifestations vary with the extent and severity of ischemic injury and, to a lesser degree, with its cause.
AMI accounts for about 0.1% of admissions to our tertiary care center. This figure has risen since the early 1980s owing to increased recognition of the disorder, an aging population, and the widespread use of intensive care units with the salvage of patients who previously would have died from cardiovascular conditions but who now survive to develop AMI as a delayed consequence of their primary disease.
Most series of AMI reported in the late 1970s and early 1980s showed that SMAE was responsible for 40% to 50%, NOMI for 20% to 30%, and SMAT for 10% to 20% of cases. The incidence of NOMI has now declined, however, likely because intensive care unit monitoring enables prompt correction of hypotension and blood volume deficits, and the widespread use of calcium channel blockers and other systemic vasodilators might protect the vascular bed from spasm. Today, SMAE is the most common cause of AMI. In one study of autopsies on patients who died from acute mesenteric thromboembolic occlusion the embolus-to-thrombus ratio was 1.4 : 1.4
Early identification of AMI requires a high index of suspicion, especially in patients older than 50 years who have long-standing congestive heart failure (particularly if the heart failure is poorly controlled), cardiac arrhythmias, recent myocardial infarction, or hypotension. The development of sudden abdominal pain in a patient with any of these risk factors should suggest the diagnosis of AMI. Younger patients, however, are not without risk of AMI, especially if they are taking vasoactive medications (e.g., phenylephrine, amphetamines, triptans), are using cocaine, or have underlying thrombophilia. Hence, unexplained, persistent, and severe abdominal pain should prompt consideration of AMI as an explanation for the pain. A history of postprandial abdominal pain in the weeks to months preceding the acute onset of severe abdominal pain is associated only with SMAT.
Almost all patients with AMI have acute abdominal pain. Early in the course of disease, the pain of AMI is far more impressive than the physical findings. Initially, the pain is severe, but the abdomen usually is flat, soft, and most often not tender, or it is less tender than expected based on the magnitude of the pain. Sudden, severe abdominal pain accompanied by rapid and often forceful bowel evacuation, especially with minimal or no abdominal signs, strongly suggests SMAE. A more indolent and less striking onset is more typical of MVT, whereas with NOMI, appreciation of abdominal pain may be overshadowed by the precipitating disorders, such as hypotension, acute congestive heart failure, acute hypovolemia, or cardiac arrhythmias. Pain is absent in as many as 25% of patients with NOMI.
Unexplained abdominal distention or gastrointestinal bleeding may be the only indications of AMI when pain is absent, especially when AMI is due to NOMI. Distention, although absent early in the course of AMI, is often the first sign of intestinal infarction. The stool contains occult blood in 75% of patients. Right-sided abdominal pain associated with the passage of maroon or bright red blood in the stool, although characteristic of colon ischemia, also may be seen with AMI, because the blood supply to the right colon and small intestine originates from the SMA. Elderly patients with AMI have been reported to develop mental confusion acutely in as many as 30% of cases.5 In patients who survive cardiopulmonary resuscitation and who then develop recurrent bacteremia or sepsis, the suspected cause of sepsis should be NOMI that resulted in a segment of bowel with subacute ischemic injury, acting as a portal for bacterial translocation.6 Although episodes of sepsis may be treated successfully with antibiotics, the length of damaged bowel must be removed to prevent recurrent sepsis.
Although abdominal findings early in the course of intestinal ischemia may be minimal or absent, increasing tenderness, rebound tenderness, and muscle guarding reflect progressive loss of intestinal viability. Such abdominal findings strongly indicate the presence of infarcted bowel. The rate of progression from the onset of abdominal pain to intestinal infarction varies not with the specific cause of ischemia but with the severity of the ischemic insult; MVT generally has a more indolent course than do the arterial causes of AMI.
On admission to the hospital, approximately 75% of patients with AMI have leukocytosis greater than 15,000 cells/mm3 and about 50% have metabolic acidemia. A normal white blood cell (WBC) count cannot be used to exclude early AMI, just as a high WBC count does not make the diagnosis. Elevated levels of serum phosphate, d-lactate, amylase, and other enzymes have been noted, as have high peritoneal fluid amylase and intestinal alkaline phosphatase activity, but the sensitivity and specificity of these markers of intestinal ischemia have not been established.7 More-specific intestinal enzymes including diamine oxidase, hexosaminidase, glutathione S-transferase,8 and intestinal fatty acid-binding protein9 also lack sufficient sensitivity and specificity to diagnose AMI. Moreover, serum markers, when elevated, usually indicate late-stage disease.
Although they are poorly sensitive (30%) and nonspecific, plain films of the abdomen still are obtained in evaluating patients with suspected AMI. Plain films of the abdomen usually are normal in AMI before infarction. Later on, formless loops of small intestine, ileus, thumbprinting of the small bowel or right colon (Fig. 114-5), or still later, pneumatosis and portal or mesenteric vascular gas may be seen. In one study, the mortality rate of patients with normal plain film studies was 29%, whereas it was 78% in those with abnormal findings.10 The primary purpose of plain films (or CT scans) is to exclude causes of abdominal pain other than ischemia that might mandate a different therapeutic approach.
CT has largely replaced plain film study of the abdomen for diagnosis and is used to identify arterial and venous thromboses as well as ischemic bowel.11–14 Findings on CT include colon dilatation, bowel wall thickening, abnormal bowel wall enhancement, lack of enhancement of arterial vasculature with timed intravenous contrast injections, arterial occlusion, venous thrombosis, engorgement of mesenteric veins, intramural gas and mesenteric or portal venous gas (Fig. 114-6), infarction of other organs, ascites, and signs related to the cause of the infarcted bowel such as hernia.11 There are three relatively specific findings of AMI that are better depicted on CT scans compared with plain films: gas in the bowel wall or portal system, acute embolic infarction of other intra-abdominal organs, and thrombi in the mesenteric vessels.12 Unfortunately, the early signs on CT are nonspecific and the late signs reflect necrotic bowel.
Figure 114-6. Computed tomography (CT) scans of a patient with acute mesenteric ischemia showing gas (arrow) in the portal veins (A) and gas (arrows) in the wall of the intestine as well as the mesentery and its vessels (B). Pneumatosis intestinalis is a late sign of ischemic injury, connotes bowel necrosis, and mandates explorative laparotomy.
In a study of 26 patients with AMI who had a preoperative multislice CT scan followed by exploratory laparotomy, CT scanning identified mesenteric arterial thrombosis in 16 of 17 patients and mesenteric vein thrombosis in 7 of 7 patients, all confirmed at operation. In this study, the sensitivity and specificity of CT scanning for occlusive AMI was 92% and 100%, respectively.15 The predictive value of CT scanning in the community might not be as high as in this report, because this study used only highly trained radiologists; improved CT scanner technology, however, likely will yield higher detection rates than in the past.
CT angiography has been shown to be promising in the diagnosis of AMI and, in one study, the added CT angiographic findings were believed to alter clinical management in 19% of 62 patients by making the diagnosis of AMI when CT alone did not.16 Magnetic resonance (MR) angiography and venography are newer imaging techniques used to diagnose AMI; they not only can image the vasculature but might be useful in determining metabolic consequences of inadequate blood flow.17,18
Laparoscopy may be useful, but it also can be misleading, because early in ischemic injury, blood may be shunted to the serosa, giving a normal appearance to the outside of the bowel even if the mucosa is necrotic. Moreover, laparoscopy is potentially dangerous because SMA blood flow decreases when intraperitoneal pressure exceeds 20 mm Hg.
Selective mesenteric angiography, often with papaverine infusion, currently is the mainstay of diagnosis and initial treatment of both occlusive and nonocclusive forms of AMI, and it should be performed promptly if AMI is suspected or diagnosed on other imaging tests. Sensitivity and specificity of mesenteric angiography for diagnosing AMI in most studies are 90% to 100% and 100%, respectively.19 Opponents of routine angiography for patients with suspected AMI cite several problems with this approach:
Proponents of angiography accept that the large number of negative angiographic studies is necessary if diagnoses are to be made early enough to improve survival. Prompt laparotomy, however, is indicated in patients with suspected AMI if angiography cannot be performed expeditiously. More controversial is the need for angiography in a patient with suspected AMI and signs of peritonitis. Because such signs usually connote infarcted bowel, the most compelling reason for angiography, namely, diagnosis of AMI while the effects of intestinal ischemia are still reversible, is no longer relevant. Angiography nonetheless still plays an important role in this situation because it can diagnose AMI and its cause and provide a roadmap for revascularization and access for serial postoperative angiographic studies.
Our approach to the management of AMI is based on several observations. First, if the diagnosis is not made before intestinal infarction, the mortality rate is 70% to 90%. Second, diagnosis of both the occlusive and nonocclusive forms of AMI can be made in most patients by angiography. Third, vasoconstriction, which can persist even after the cause of the ischemia is corrected, is the basis of NOMI and a contributing factor in the other forms of AMI. Finally, vasoconstriction can be relieved by vasodilators infused into the SMA. The cornerstones of our approach, therefore, are the earlier and more liberal use of angiography and the incorporation of intra-arterial papaverine in the treatment of both occlusive AMI and NOMI. Duration of symptoms parallels mortality, and therefore early diagnosis and treatment is paramount to increase the chance for survival.20
AMI should be suspected in patients older than 50 years who have the risk factors previously described and in younger patients—especially those with atrial fibrillation, vasculitis, a coagulation disorder, and those on vasoactive medications—who seek medical attention for sudden, severe abdominal pain that lasts longer than several hours. These patients should be managed according to the algorithm shown in Figure 114-7. Less-absolute indications for inclusion into this protocol consist of unexplained acute abdominal distention, colonoscopic evidence of isolated right-sided colonic ischemia, and acidosis without an identifiable cause.
Figure 114-7. Algorithm for the diagnosis and treatment of intestinal ischemia. CTA, computed tomographic angiogram; DVT, deep venous thrombosis; SMA, superior mesenteric artery. Solid lines show conventional management plan; dotted lines show alternative management plan.
(Modified from Brandt LJ, Boley SJ. AGA technical review on intestinal ischemia: American Gastrointestinal Association. Gastroenterology 2000; 118:954; corrected version in Gastroenterology 2000; 119:281.)
Initial management of patients with suspected AMI includes resuscitation and diagnostic imaging studies. Resuscitation includes relief of acute congestive heart failure and correction of hypotension, hypovolemia, and cardiac arrhythmias. Broad-spectrum antibiotics (e.g., levofloxacin, metronidazole, piperacillin-tazobactam) are given immediately because of the high incidence of positive blood cultures in AMI and because they reduce the extent and severity of ischemic injury in experimental animals.21 There are no randomized, controlled trials showing the benefit of antibiotics in AMI, and it is unlikely that such trials will ever be done. After resuscitation, plain films or CT scan of the abdomen are obtained, not to establish the diagnosis of AMI but rather to exclude other causes of abdominal pain. A normal plain film or CT scan does not exclude AMI; ideally, patients are studied before radiologic signs appear because these signs connote irreversibly damaged bowel. If no alternative diagnosis is made on these studies, selective SMA angiography is performed. Based on the angiographic findings and the presence or absence of peritoneal signs, the patient is treated according to the algorithm in Figure 114-7.
Even when the decision to operate has been based on clinical grounds, preoperative angiography should be performed to manage the patient properly at and after laparotomy. Relief of mesenteric vasoconstriction is essential to the treatment of emboli, thromboses, and the nonocclusive low-flow states. Infusion of the phosphodiesterase inhibitor papaverine, through the angiography catheter in the SMA, is used to relieve mesenteric vasoconstriction preoperatively and postoperatively. The papaverine is infused by pump at a constant rate of 30 to 60 mg/hr; papaverine concentrations may vary with the need for fluid restriction.
Although most of the papaverine infused into the mesenteric bed is cleared during one pass through the liver, blood pressure and cardiac rate and rhythm must be monitored constantly. Some patients with liver disease exhibit a drop in blood pressure with this dose of papaverine, but the most common cause of hypotension during the papaverine infusion is dislodgment of the catheter. In patients who have a sudden drop in blood pressure, the papaverine should be replaced with saline or glucose solution and a plain film image of the abdomen should be promptly performed to confirm the catheter’s location. If the catheter has come out of the SMA, it should be replaced and the papaverine should be restarted. The patient’s clinical and angiographic responses to the vasodilator determine the duration of therapy.
Laparotomy is performed in AMI to restore arterial flow obstructed by embolus or thrombosis or to resect irreparably damaged bowel, or both. Embolectomy, thrombectomy, or arterial bypass precedes evaluation of intestinal viability because bowel that initially appears infarcted can show surprising recovery after adequate blood flow is restored. In the operating room, intestinal viability can be assessed clinically, by qualitative or quantitative surface fluorescence or by Doppler ultrasonography.22 Animal models show that administration of intravenous glucagon, intravenous heparin-binding epidermal growth factor (HB-EGF)-like growth factor or intraluminal nitroglycerin after revascularization of an acute arterial occlusion can improve mucosal viability and minimize reperfusion damage.23,24
In practice, glucagon is sometimes used because of its accessibility and anecdotal beneficial effects despite lack of strong supporting data from human trials. Short segments of bowel that are nonviable or questionably viable after revascularization are resected, and a primary anastomosis is performed. If extensive portions of the bowel are of questionable viability, however, only the clearly necrotic bowel is resected and re-exploration (second look) is planned for within 12 to 24 hours. The interval between the first and second operations is used both to allow better demarcation between viable and nonviable bowel and to attempt to improve intestinal blood flow by using intra-arterial papaverine and by maximizing cardiac output.
The use of anticoagulants in the management of AMI is controversial. Anticoagulation with heparin can cause intestinal or intraperitoneal hemorrhage and, except for MVT, should not be used routinely in the immediate postoperative period; 48 hours after embolectomy or arterial reconstruction, when thrombosis is common, anticoagulation is appropriate.
SMAE is responsible for 40% to 50% of AMI episodes. Emboli usually originate from a left atrial or ventricular mural thrombus. Many patients with SMAE have had previous peripheral artery emboli, and approximately 20% have synchronous emboli. SMAEs lodge at points of normal anatomic narrowing, usually immediately distal to the origin of a major branch. Angiography typically reveals a rounded filling defect with nearly complete obstruction to flow. Mesenteric atherosclerosis is usually not as severe as in SMAT. Emboli proximal to the origin of the ileocolic artery are considered major emboli. Minor emboli are those that lodge in the SMA distal to the takeoff of the ileocolic artery or in the distal branches of the SMA (Fig. 114-8).
Figure 114-8. A, Superior mesenteric artery (SMA) angiogram in a 71-year-old man with abdominal pain showing an embolus occluding the SMA at the level of the origin of the right colic artery (arrow). Vasoconstriction is noted distal to the embolus. B, Repeat angiogram done 54 hours after SMA embolectomy and preoperative and postoperative papaverine infusions into the SMA. Vasodilatation is seen, and all vessels are patent except for a distal jejunal branch, which contains a piece of the inciting embolus (arrowhead) that broke off during the course of vasodilator therapy because of endogenous thrombolysis. Papaverine protected the bowel within the distribution of the embolized vessel by enabling vasodilatation and maintenance of adequate blood flow.
Various therapeutic approaches have been proposed for SMAE, depending on the presence or absence of peritoneal signs, whether the embolus is partially or completely occluding, and whether the embolus is above the origin of the ileocolic artery or more distal. Therapy for SMAE has included surgical revascularization, intra-arterial perfusion with vasodilators or thrombolytic agents, and anticoagulation.19 In the absence of peritoneal signs, minor SMA emboli have been treated successfully with all of these agents without the need for surgery. Exploration is usually performed in patients with major emboli after papaverine infusion is begun. Nonoperative therapy using only papaverine infusion is attempted if there are significant contraindications to surgery, no peritoneal signs, and adequate perfusion of the vascular bed distal to the embolus after a bolus of vasodilator into the SMA.
Exploratory laparotomy is mandatory when peritonitis is present; embolectomy and bowel resection are performed as necessary. If possible, intra-arterial papaverine is begun before surgery and is continued during surgery. If no “second-look” operation is planned, infusion is continued for 12 to 24 hours postoperatively; persistent vasospasm is excluded by angiography before the catheter is removed (see Fig. 114-8). If a second operation is planned, the infusion is continued through the second procedure until angiography shows the vasoconstriction is ceased. Recognition of persistent vasoconstriction has prompted some authorities to recommend routine use of intra-arterial papaverine in all patients with SMAE; the best survival rates are seen in patients treated by this approach.19
Use of transcatheter thrombolytic therapy (e.g., alteplase or urokinase) can be considered before exploratory laparotomy if the patient does not have signs of peritonitis. Prospective studies and meta-analyses have shown that thrombolysis may be effective in resolving thrombi, improving symptoms, and avoiding surgery in patients with lesions amenable to such therapy.25,26 Thrombolytic therapy is most likely to be successful when the embolus is partially occluding or is minor and when the study is performed within 12 hours of the onset of symptoms.27 A canine study showed that intra-arterial streptokinase was more effective than intra-arterial papaverine in lysing clots implanted into the SMA, although greater ischemic damage occurred with streptokinase than with papaverine because of papaverine’s action to cause vasodilation and open collateral pathways for blood flow around the obstructing clot. When streptokinase and papaverine were administered simultaneously, neither medication functioned as well as it did alone and intestinal damage was intensified.28 Given the shortage of supporting evidence for thrombolytics in AMI and the high complication rate attending their use, this treatment remains controversial.27
NOMI is responsible for 20% to 30% of AMI and usually is due to splanchnic vasoconstriction consequent to a preceding cardiovascular event. AMI can appear hours to days after the event, and vasoconstriction, which initially is reversible, can persist even after the precipitating event has been corrected. Precipitating causes for NOMI include acute myocardial infarction, congestive heart failure, arrhythmias, shock, cirrhosis, medications (e.g., digitalis), cardiopulmonary bypass surgery, and chronic kidney disease, especially when patients are on either hemodialysis or peritoneal dialysis. When presenting with abdominal pain, patients on peritoneal dialysis may be thought to have peritonitis, thereby delaying the diagnosis of NOMI and resulting in a poor outcome.29
NOMI is diagnosed by angiography using four criteria: narrowing of the origins of SMA branches, irregularities in the intestinal branches, spasm of the arcades, and impaired filling of intramural vessels. Patients with these signs who are neither in shock nor on vasopressors and who do not have pancreatitis can be considered to have NOMI (Fig. 114-9).
Figure 114-9. Superior mesenteric angiogram in a patient with nonocclusive mesenteric ischemia (NOMI) following a bout of gastrointestinal hemorrhage and shock. A, The pretreatment film shows the diffuse vasoconstriction of NOMI. B, Marked vasodilatation is evident on the repeat study after 48 hours of an intra-arterial papaverine infusion.
(From Brandt LJ, Boley SJ. Ischemic intestinal syndromes. Adv Surg 1981; 15:1.)
SMA infusion of papaverine is begun as soon as the diagnosis is made. Operation is performed if peritoneal signs are present, and the infusion is continued during and after exploration. Necrotic bowel is resected; it is better to leave bowel of questionable viability and perform a second-look operation than to perform massive enterectomy, because compromised but viable bowel often improves with supportive measures. The infusion is continued as for second-look operations following embolectomy.
When papaverine infusion is used as the only treatment for NOMI in patients without signs of peritonitis, it is continued for 24 hours, and repeat angiography is performed 30 minutes after changing the papaverine infusion to normal saline. Papaverine infusion is maintained and angiography repeated daily until there is no roentgenographic evidence of vasoconstriction and the patient’s clinical findings resolve. Infusions, usually discontinued after 24 hours, have been given for as long as 5 days.
Acute SMAT occurs in areas of severe atherosclerotic narrowing, most often at the origin of the SMA. The acute ischemic episode may be superimposed on chronic mesenteric ischemia (CMI), and 20% to 50% of patients have a history of postprandial abdominal pain and weight loss during the weeks to months preceding the acute event. Evidence of coronary, cerebrovascular, or peripheral arterial insufficiency is common.
SMAT is demonstrated on flush aortography, which usually shows occlusion of the SMA 1 to 2 cm from its origin. Some distal filling of the SMA via collaterals is common. Branches proximal and distal to the obstruction can show localized or diffuse vasoconstriction. In patients with abdominal pain, no abdominal tenderness, and complete occlusion of the SMA on aortography, it is important, though difficult, to distinguish between acute thrombosis and long-standing, coincidental chronic occlusion. Prominent collaterals between the SMA and other major splanchnic vessels indicate chronic SMA occlusion. If there is good filling of the SMA, the occlusion is considered chronic and the abdominal pain is considered unrelated to mesenteric vascular disease (see Fig. 114-4). The absence of collateral vessels or the presence of collaterals with inadequate filling of the SMA indicates an acute occlusion and demands prompt intervention. If possible, an angiographic catheter is placed in the proximal SMA, and papaverine infusion is begun before surgery is undertaken.
At surgery, necrotic bowel is resected and remaining bowel is revascularized. Papaverine infusion is continued throughout the operative period, and management is the same as for SMAE. There are only a few reports of use of thrombolytic agents or percutaneous angioplasty for SMAT.
Complications of angiography and prolonged infusion of vasodilator drugs include transient acute tubular necrosis following angiography, local hematomas at the arterial puncture sites, catheter dislodgment, and fibrin clots on the arterial catheter. Infusion for more than 5 days has not had significant systemic effects.
Although mortality rates of 70% to 90% were reported through the 1980s for patients whose AMI was diagnosed and treated conventionally, the approach described here can reduce these catastrophic figures. The best survival is reported in series in which angiography has been used routinely in the management of AMI.30–35
In our tertiary medical center, more than 50% of the patients with AMI treated according to our approach survived, and more than 75% have lost less than one meter of intestine. The importance of early diagnosis is emphasized by the survival of 90% of patients who had AMI but no signs of peritonitis, and who had angiography early in their course. Ideally, all patients with AMI should be studied when plain films of the abdomen and CT scanning are normal and before signs of an acute surgical abdomen and laboratory evidence of infarction appear. Diagnosis before intestinal infarction occurs is the most important factor in improving survival of patients with AMI.
MVT occurs as an acute, subacute, or chronic disorder. It is only since the development of recent imaging techniques that these various forms of MVT have been recognized; previously, only acute MVT was known, and diagnosis was made at laparotomy or autopsy.
In early studies, MVT was believed to be the major cause of AMI, but most of these cases probably represented NOMI. Today, only 5% to 10% of patients with AMI have MVT. The mean age at presentation with MVT is in the mid-60s.36 A Swedish study showed that the highest incidence of MVT was 11.3 per 100,000 person years among those 70 to 79 years old.37
Previously, a cause of MVT was identified in fewer than half of patients. The discoveries of the primary and secondary hypercoagulable states and the use of estrogens for contraception and hormone replacement have led to identification of the cause in almost 90% of patients.38 Arterial hypertension is the most commonly associated medical comorbidity with this disorder, and neoplasms (e.g., acute lymphocytic leukemia, adenocarcinoma of the pancreas, stomach) and coagulation disorders (e.g., lupus anticoagulant, factor V Leiden, and protein S deficiency) also are commonly seen.36,39 A list of predisposing conditions for MVT is given in Table 114-3.