Part06 Ch04 Copy

8/16/2019 Part06 Ch04 Copy

1/12

VASCULAR SYSTEM ACUTE MESENTERIC ISCHEMIA — 1

DOI 10.2310/7800.S06C0401/10

ACUTE MESENTERIC ISCHEMIA Melina R. Kibbe, MD, and Heitham T. Hassoun, MD

Acute mesenteric ischemia is an uncommon life-threateningclinical entity that ultimately leads to death unless it isdiagnosed and treated appropriately. Despite diagnostic andtherapeutic advances and an improved understanding of thepathophysiology, the morbidity and mortality associatedwith acute mesenteric ischemia remain high, having changedrelatively little over the past several decades. Accordingly, theindex of suspicion for this disease should be high whenever apatient presents with acute-onset severe abdominal pain thatis out of proportion to the physical ndings. Once the diag-

nosis is made, prompt intervention is required to minimizemorbidity and mortality.

Acute mesenteric ischemia can result from any of fourdistinct processes: (1) embolic occlusion of the mesentericcirculation (usually the superior mesenteric artery [SMA]);(2) acute thrombosis of the mesenteric circulation; (3) intensesplanchnic vasoconstriction—so-called nonocclusive mesen-teric ischemia (NOMI)—which is usually associated with alow-ow state or profound hypovolemia; or (4) mesentericvenous thrombosis (MVT).

Clinical Evaluation

The classic presentation forpatients with embolic disease of themesenteric vessels is sudden-onsetmidabdominal pain that is describedas being out of proportion to thephysical ndings and is associatedwith immediate bowel evacuation.In fact, only about one third of patients present withthe triad of abdominal pain, fever, and heme-positive stools.A study that considered all causes of acute mesenteric isch-emia found that 95% of patients presented with abdominalpain, 44% with nausea, 35% with vomiting, and 35% withdiarrhea 1; only 16% presented with blood per rectum.

Patients with thrombotic mesenteric occlusion also presentwith sudden-onset severe midabdominal pain that is out ofproportion to the physical ndings, but unlike patients withacute embolic occlusion, they typically have a history of chronicpostprandial abdominal pain and signicant weight loss.

Patients with NOMI present somewhat differently. Thepain reported is usually not as sudden as that noted withembolic or thrombotic occlusion: it is generally more diffuseand tends to wax and wane, unlike the pain associatedwith embolic or thrombotic disease, which tends to getprogressively worse.

Patients with MVT often present with various nonspecicabdominal complaints; accordingly, this diagnosis may beespecially challenging. Common complaints include nausea,vomiting, diarrhea, abdominal cramping, and nonlocalizedabdominal pain. As a rule, these symptoms are not acute.A study of MVT patients found that 84% presented withabdominal pain. 2 Of those 84%, only 16% presented withperitoneal signs, whereas 68% presented with vague abdomi-nal pain. Other presenting symptoms included diarrhea(42%), nausea and vomiting (32%), malaise (16%), and

upper gastrointestinal bleeding (10%). 2In addition to the clinical presentation, risk factors provide

essential clues for correct identication of these diseaseprocesses. Certain general risk factors for acute mesentericischemia have been identied. In one study, 78% of thepatients presented with a history of hypertension, 71% witha history of tobacco use, 62% with a history of peripheralvascular disease, and 50% with a history of coronary arterydisease (CAD). 1 Acosta-Merida and colleagues found thatthe presence of cardiac illness, elevated plasma urea levels,and both small and large bowel involvement independentlypredicted perioperative mortality. 3

There are also more specic risk factors for individualcauses of acute mesenteric ischemia. Patients with embolicocclusion of the mesenteric circulation typically have ahistory of recent cardiac events (e.g., myocardial infarction,atrial brillation, mural thrombus, mitral valve disease, or leftventricular aneurysm) or previous embolic disease. In thestudy just cited, 50% of the patients who presented withembolic occlusive disease had atrial brillation. 1 Patients withacute mesenteric ischemia secondary to thrombotic occlusivedisease typically have other manifestations of diffuse athero-sclerotic disease (e.g., CAD, peripheral artery disease, andcarotid stenosis). The risk factors for NOMI are slightlydifferent. This condition usually occurs during severe low-ow states and represents extreme mesenteric vasoconstric-tion. It is much more common among severely ill patientsin an intensive care unit (ICU) who require vasopressorsand among patients undergoing dialysis with excessive uidremoval. The risk factors for MVT include a history of previ-ous venous thrombosis or pulmonary embolism, a known orsuspected hypercoagulable state, oral contraception, andestrogen supplementation. In a study of 31 patients whopresented with MVT at Northwestern University, 13 (42%)were diagnosed with a hypercoagulable state, six (19%) hada history of previous thrombotic episodes, and four (13%)had a history of cancer. 2

Diagnosis and Management of Acute Bowel Ischemia

© 2010 Decker Intellectual Properties Inc American SurgeryScientific

8/16/2019 Part06 Ch04 Copy

2/12

ACUTE MESENTERIC ISCHEMIA — 2

01/10

Obtain history and perform physical examination. Pain that is out of proportionto physical findings is a significant clue.Look for risk factors for acute mesenteric ischemia.Order investigative studies:• Laboratory tests: WBC count, lactate, AST• Imaging: abdominal x-ray, duplex ultrasonography, CT angiography, MRA

Patient presents with severe abdominal pain consistent withischemic bowel

Manage underlying disorder as appropriate.

Treat with surgical embolectomy

and anticoagulation.Consider catheter-directedintra-arterial thrombolysis.Assess bowel for possibleresection.

Specific disorder is identified

No bowel resection wasrequired, and bowel isviable after revascularization

Patient has embolic disease

Perform mesenteric bypass,

either antegrade (from supraceliacaorta to SMA) or retrograde(from infrarenal aorta or iliacartery to SMA).Assess bowel for possibleresection.

Patient has thrombotic disease

Correct underlying condition.Optimize fluid status, improvecardiac output, and eliminatepressors.Consider catheter-directed intra-arterial infusion of papaverine,30–60 mg/hr. Assess therapywith repeat angiography.

Patient has nonocclusivemesenteric ischemia (NOMI)

Treat with anticoagulation.Consider catheter-directedthrombolysis.Perform hypercoagulabilityworkup.

Patient has mesentericvenous thrombosis (MVT)

Perform second-look exploratory

laparotomy.

Bowel resection was required,or there is marginally perfusedbowel after revascularization

Patient improves andshows no signs of bowelischemia

Perform exploratory laparotomy,and resect any frankly necroticbowel.Perform second-look exploratorylaparotomy to assess viability ofany marginally perfused bowel.

Patient does not improveor shows signs of bowelischemia

Perform contrast angiography (anteroposteriorand lateral views; early and delayed images) to

confirm diagnosis.

Acute mesenteric ischemia is suspected

Diagnosis and Management of Acute Bowel Ischemia

VASCULAR SYSTEM© 2010 Decker Intellectual Properties Inc American SurgeryScientific

8/16/2019 Part06 Ch04 Copy

3/12


01/10

Lastly, the importance of prompt surgical evaluationand diagnosis cannot be overemphasized. Given the oftennonspecic presentation of patients with acute mesentericischemia, the diagnosis is delayed in many patients. Eltarawyand colleagues found that a delay in surgical consultation ofmore than 24 hours after the onset of symptoms resulted ina statistically signicant increase in mortality, with an oddsratio of 9.4. 4 Furthermore, a delay in operation of more than6 hours following surgical consultation was also associatedwith an increase in mortality, with an odds ratio of 4.9.Interestingly, the authors found that patients who presentedwith abdominal distention, elevated lactate, acute renalfailure, vasopressor administration, and a lack of abdominalpain were more likely to have a delay in surgical consultation.Thus, having a heightened awareness of acute mesentericischemia may lead to more prompt surgical consultation,diagnosis, and treatment and may improve patient outcomes.

Investigative Studies

Although there are no basic laboratory or radiographicstudies that are diagnostic for acute mesenteric ischemia,such studies can help conrm the diagnosis when it issuspected on the basis of the history and the physicalexamination.

In most cases, the white blood cell count is elevated. In astudy from the Mayo Clinic, 98% of patients who presentedwith acute mesenteric ischemia were found to have anelevation of the leukocyte count, and 50% were found to havecounts higher than 20,000/µL. 1 Lactate is another nonspecicindicator of mesenteric bowel ischemia. In the same MayoClinic study, approximately 91% of patients had elevatedlactate levels, with 61% having levels higher than 3 mmol/L.In addition, 71% of patients presented with an elevatedaspartate aminotransferase, whereas 52% presented with anabnormal base decit. 1 D-dimer is another test that hasbeen suggested to aid in the diagnosis of acute mesentericischemia. 5 However, recently Akyildiz and colleagues demon-strated that whereas the sensitivity of D-dimer testing for thediagnosis of acute mesenteric ischemia was 94.7%, the spec-icity was only 78.6% as many other pathologies may resultin a rise in D-dimer levels. 6 Thus, this test should be usedwith caution.

Abdominal X-rays

Although abdominal radiographic lms can neither estab-lish nor exclude the diagnosis of acute mesenteric ischemia,

they may reveal signs that are consistent with bowel ischemia.If obtained early, abdominal plain lms should show noabnormalities. If obtained late in the presentation, however,they may reveal edematous bowel with thumbprinting. Insevere cases, abdominal plain lms may reveal gas in thebowel wall and the portal vein. More commonly, however,they reveal a pattern consistent with ileus or are completelyunremarkable. In a study of patients operated on for acutemesenteric ischemia, mortality was 29% in patients withnormal plain radiographic lms, compared to 78% in those

with abnormal lms. 7 Nevertheless, it must be emphasizedthat the primary role of abdominal plain radiographic lms inthis setting is to exclude other identiable causes of abdominalpain (e.g., obstruction and perforation with free air).

Duplex Ultrasonography

Although duplex ultrasonography does have a deniteand well-dened role in the diagnosis of chronic mesentericischemia, it plays only a limited role in the management of

acute mesenteric ischemia. This is not surprising given theacute nature of the presentation, the accompanying ileuswith excessive bowel gas and bowel edema (which hindersvisualization of the mesenteric vessels), and the reducedaccess to the vascular laboratory during off-hours. Further-more, duplex ultrasonography, although capable of imagingstenotic and occlusive lesions at the origin of a mesentericvessel, is of little value in detecting emboli beyond the proxi-mal portion of the vessel. Similarly, it has a limited role in thediagnosis of NOMI.

Computed Tomographic Angiography

Computed tomographic (CT) angiography and magneticresonance angiography (MRA) are more commonly used to

conrm the diagnosis of acute mesenteric ischemia thanduplex ultrasonography is. Both CT and MRA have under-gone signicant advances over the past decade. TraditionalCT scanning can evaluate arterial patency and anatomyand detect calcications and aneurysms. In addition, itcan evaluate the status of the bowel and help identify othercauses of abdominal pain (e.g., pancreatitis, bowel perfora-tion, and bowel obstruction). However, it was not until theadvent of helical (spiral) CT scanning—and, subsequently,of multislice, multiarray helical CT scan technology withmaximum-intensity projection—that the visceral arterialanatomy could be visualized with three-dimensional spatialresolution [ see Figure 1 ]. This technology allows much morerapid acquisition of data and thereby improves the quality

of vascular imaging tremendously. A study comparing spiralCT angiography with conventional contrast angiographyfound that the former had a sensitivity of 75% and a specic-ity of 100% for the detection of greater than 75% stenosis ofthe celiac artery. 8 Furthermore, spiral CT angiography had asensitivity of 100% and a specicity of 91% for the detectionof SMA stenosis. More recent studies with multidetector16-row CT angiography have revealed a sensitivity and spec-icity of 96.4% and 97.9%, respectively, in diagnosing acutemesenteric ischemia and an overall accuracy of 95.6%. 9,10 Thus, multidetector CT angiography is a useful tool for fastand accurate diagnosis of acute mesenteric ischemia.

Although CT technology has become much more sophisti-cated and the image clarity and denition have improved

greatly, there are still limits that warrant discussion to whatcan be determined by means of CT in the setting of acuteembolic or thrombotic disease. The origins of the celiacartery and the SMA are well visualized with CT, but second-ary, tertiary, and smaller branches are less well dened; forvisualizing these branches, contrast angiography remains thegold standard [ see Contrast Angiography, below]. Anotherlimitation of current CT scanning technology is the need toadminister intravenous (IV) contrast agents, which can benephrotoxic or, in some patients, trigger contrast allergies.


8/16/2019 Part06 Ch04 Copy

4/12


01/10

CT angiography also tends to overestimate the degreeof critical stenosis when compared with conventional angio-graphy; however, this limitation appears to be less of an issuewith the advent of multiarray or multidetector technology,which is more sensitive in detecting arterial stenosis. Finally,signicant calcication at the origin of the vessel can make itdifcult to determine the true degree of stenosis with CTscanning.

In contrast to its relatively limited role in the diagnosisof acute mesenteric ischemia of embolic or thromboticorigin, CT plays a valuable role in diagnosing MVT and isthe preferred diagnostic imaging modality in patients present-ing with abdominal pain who have a history of deep vein

thrombosis or a known hypercoagulable disorder. 11 CT scan-ning can readily reveal thrombosis of the superior mesentericvein (SMV), with or without associated bowel abnormalities[see Figure 2 ]. In fact, CT scans of SMV thrombosis in asymp-tomatic patients have provided useful information on thepathophysiology of MVT and broadened our understandingof the wide spectrum of this disease entity. In a study fromthe Mayo Clinic, CT scanning correctly identied 100% ofpatients who presented with acute MVT and 93% of thosewho presented with chronic venous thrombosis. 12 In a sub-sequent study from our institution (Northwestern Univer-sity), CT scanning identied 100% of MVT patients whopresented with vague abdominal pain or diarrhea and 90%

Figure 1 Shown are computed tomography scans of mesenteric vessels: ( a ) transaxial image of celiac artery ( arrow ); ( b )transaxial image of the superior mesenteric artery (SMA) ( arrowhead ); and ( c ) three-dimensional reconstruction of aorta andorigins of celiac artery ( arrow ) and SMA ( arrowhead ).

Figure 2 ( a ) Computed tomography (CT) scan shows partially occluding thrombus in the superior mesenteric vein (SMV)( arrow ). ( b ) CT scan obtained 4 months later reveals complete resolution of thrombus ( arrowhead ).


8/16/2019 Part06 Ch04 Copy

5/12

8/16/2019 Part06 Ch04 Copy

6/12

8/16/2019 Part06 Ch04 Copy

7/12


01/10

Percutaneous interventional treatment of acute SMA occlu-sion has also been described in the literature. At present,however, the applicability of this approach is limited in thatmost patients present with symptoms that warrant an explor-atory laparotomy for evaluation of intestinal viability. In

patients who present with abdominal pain, have no peritonealsigns that would necessitate an immediate exploratory lapa-rotomy, and are found to have a partially occluding embolusin the SMA, catheter-directed intra-arterial thrombolytictherapy is worth considering. Demirpolat and colleaguesreported performing mechanical thrombus fragmentation inthree such patients with good success. 14 We have treated afew patients with partially occlusive emboli and no peritonealsigns on presentation at our institution using endovascularapproaches. This route should be used cautiously, however,and if intra-arterial thrombolytic therapy is instituted, thepatient should be closely monitored in the ICU with serialabdominal examinations. Even if thrombolytic therapy doesrestore blood ow to the ischemic intestine, the patient maystill experience pain sufcient to necessitate exploration.For these reasons, our use of thrombolytic therapy is highly

selective.Thrombotic Occlusion of MesentericVessels

Acute mesenteric ischemia sec-ondary to thrombotic disease occursin patients with long-standing ath-erosclerotic disease of the mesen-teric vessels. In this situation, theentire midgut is usually involved.

Figure 7 Shown are contrast angiograms of aorta and mesenteric vessels in a patient with nonocclusive mesenteric ischemia.( a ) Selective angiogram (anterior projection) of the superior mesenteric artery (SMA) demonstrates distal spasm of SMA.( b ) Selective angiogram (anterior projection) of SMA after intra-arterial papaverine infusion demonstrates improved lling ofdistal branches of SMA.

Figure 8 ( a ) Selective angiogram of the superior mesentericartery demonstrates partially occluding embolus in distalvessel ( arrow ). ( b ) Selective angiogram after catheter-directed intra-arterial thrombolytic therapy shows resolutionof embolus.

a b


8/16/2019 Part06 Ch04 Copy

8/12

8/16/2019 Part06 Ch04 Copy

9/12


01/10

Figure 9 Algorithm illustrates intraoperative determination of bowel salvageability, evaluation of the superior mesentericartery (SMA) pulses, and assessment of bowel viability after revascularization. MVT = mesenteric venous thrombosis;NOMI = nonocclusive mesenteric ischemia.

Determine whether bowel is salvageable. About 50 cm of viable bowel is required tosustain life if ileocecal valve is present; 100 cm is preferred.

Surgeon is consulted intraoperatively for evaluation of acute mesenteric ischemia

Assess pulses in SMA.

Bowel is salvageable

Correct underlying condition.Optimize fluid status, improvecardiac output, and eliminatepressors.Consider catheter-directed intra-arterial infusion of vasodilator.assess bowel for possibleresection.

NOMI is likely diagnosis

Treat with surgical embolectomyand anticoagulation.Assess bowel for possibleresection.

Embolic disease of SMA islikely diagnosis

Perform second-look exploratory laparotomy.

Bowel resection was required, or there ismarginally perfused bowel after revascularization

Bowel is viable

Perform mesenteric bypass,either antegrade (fromsupraceliac aorta to SMA) orretrograde (from infrarenalaorta or iliac artery to SMA).Assess bowel for possibleresection.

Thrombotic disease ofSMA is likely diagnosis

Begin anticoagulation immediately.Determine underlying cause.Perform hypercoagulability workup.Assess bowel for possible resection.

MVT is likely diagnosis

Close abdomen.

Bowel is not salvageable

No pulse is felt in SMA Weak pulse is felt in SMA

Proximal jejunum andtransverse colon are sparedfrom ischemia

Diffuse midgut bowelischemia is present

Normal pulse is felt in SMA

Intraoperative Consultation

Vascular surgeons are frequently consulted intraoperativelyto evaluate a patient for acute mesenteric ischemia. Oftenthe patient has been taken to the OR on an emergency basisfor acute abdominal pain with peritoneal signs or hemody-namic instability [ see Figure 9 ]. In the OR, acute mesentericischemia typically presents as diffuse bowel ischemia. Therst decision point in the evaluation is the determination ofwhether the bowel is salvageable.

Determination of Bowel Viability

If diffuse bowel necrosis exists and the bowel is not salvage-able, it is best to close the abdomen without attempting

further therapy. Approximately 50 cm of viable bowel isrequired to sustain life if the ileocecal valve is present, and100 cm is preferable. 20 Therefore, if it is obvious that nobowel can be preserved, further intervention is pointless. Ifthe bowel is salvageable, blood ow to the bowel is evaluatedby assessing the pulses and/or Doppler signals in the SMA.If no pulse can be detected in the SMA, revascularizationshould be undertaken before bowel resection.

SMA pulses are assessed by palpating the root of the

mesentery. The transverse colon is reected superiorly, andthe small bowel is reected to the patient’s right. The SMAis then palpated by placing four ngers of the hand behind


8/16/2019 Part06 Ch04 Copy

10/12


01/10

by underlying atherosclerotic lesions. In NOMI, the entire

small bowel may be affected, but the pattern of ischemiatends to be patchy, with segmental areas of involvement.

Approximately 10 to 20 minutes after revascularization, theviability of the intestine should be assessed. Waiting untilafter revascularization to assess the extent of irreversiblebowel ischemia or necrosis requiring resection makes it pos-sible to preserve more bowel length. After restoration ofow, the bowel may contain frankly necrotic areas, normalareas, and marginally perfused areas. Obviously, clearlynecrotic or nonviable bowel must be resected at the time ofthe operation. Determination of the viability of marginallyperfused bowel is more difcult.

Intraoperatively, the color, motility, and integrity of thebowel should be evaluated. The characteristic appearance ofischemic bowel includes loss of the normal sheen, dull-graydiscoloration, and lack of peristalsis. Determination of thecharacter and quality of the pulses in the antimesentericborder and the mesenteric arcades may help determine whichareas of the bowel will remain viable once revascularizationhas been performed. Intraoperative Doppler assessmentof bowel perfusion may be performed with a sterilizedcontinuous-wave Doppler ultrasound ow detector. Theprobe is placed on the antimesenteric border of the intestineto detect pulsatile Doppler signals. Even in the best of hands,

however, this technique remains unreliable in predictingsubsequent bowel viability.Other diagnostic options include IV administration of uo-

rescein, transcutaneous oxygen measurement, and second-look exploratory laparotomy. All of these measures arerelatively simple to perform, but each has limitations.

the root of the mesentery, with the thumb opposite and ante-rior to the root. The SMA can also be identied by followingthe middle colic artery proximally until it enters the SMA.Alternatively, a handheld Doppler device may be employedto listen to the quality and character of the arterial signal atthe root of the mesentery. It is important to palpate the SMApulse distally as well as proximally to ensure that the patientdoes not have an embolus to the distal SMA. Intraoperativeangiography may also be used for evaluation, but it is oftendifcult to perform in the OR if there has not been adequatepreparation and setup ahead of time, and it may not befeasible in some institutions.

If a strong pulse is appreciated throughout the length ofthe SMA, MVT is the probable cause of the diffuse bowelischemia. Once MVT is suspected, IV administration ofheparin should immediately follow. If the SMA pulse is pres-ent but weak, the diagnosis of NOMI should be entertained.However, if there is no SMA pulse at the root of the mesen-tery, the most likely diagnosis is in situ thrombosis fromchronic mesenteric arterial disease [ see Figure 4 ]. If the SMApulse is palpable proximally but not several centimetersdistally, the likely diagnosis is an embolus to the SMA [ see

Figure 4 ]. Distinguishing between these two conditions isimportant because their surgical treatments differ signi-cantly. To make this distinction correctly, the surgeon shouldbe aware of how the patient presented, whether the patientexperienced postprandial abdominal pain for an extendedperiod before the acute presentation, and whether the patienthas other risk factors of arterial occlusive disease [ see ClinicalEvaluation, above ]. In addition, the surgeon should be awareof the specic pattern of bowel ischemia present.

The different causes of acute mesenteric ischemia areassociated with different classic patterns of bowel ischemia,which must be distinguished from one another. The basicdistinction between arterial and venous pathologic conditionsis relatively simple. In mesenteric ischemia resulting fromvenous disease, the bowel typically is diffusely edematous,congested, and dilated. In mesenteric ischemia resulting fromarterial disease, the small bowel is typically contracted duringthe early phase of presentation, although it may be dilatedand edematous when the patient presents late with frankbowel necrosis.

Within the category of arterial causes of acute mesentericischemia, the various underlying conditions are also associ-ated with distinct patterns of bowel ischemia. Typically, inembolic disease, the small bowel and the proximal colon areaffected, and the proximal jejunal segment and the transverse

colon are spared [ see Figure 10 ]; the reason is that the embolususually lodges just past the middle colic artery and the jejunalbranches of the SMA. If the entire small bowel is diffuselyaffected, as well as the ascending and transverse colon,the origin of the SMA is probably occluded; this diseasepattern is consistent with thrombotic occlusion of the vessel

Figure 10 Intraoperative photograph of patient whopresented with acute mesenteric ischemia secondary toembolus of the superior mesenteric artery shows diffuse bowelischemia with classic sparing of proximal jejunum ( arrow )and transverse colon ( arrowhead ).


8/16/2019 Part06 Ch04 Copy

11/12


01/10

Discussion

inammatory events) are major contributing factors. Theapplication of more broad-based therapeutic modalities suchas regional controlled hypothermia for organ protectionduring ischemia may alleviate these aforementioned limita-tions and prove yet to be efcacious in the clinical setting. 37,38 Nonetheless, it is likely that to achieve any meaningfulimprovements in our ability to treat patients with acutemesenteric ischemia, we will have to expand our knowledgeof the early molecular pathways involved in the activation andproliferation of both local and systemic inammation.

Outcome after Surgical Treatment

Most studies that include a large number of patients withacute mesenteric ischemia report perioperative mortalities rang-ing from 32 to 69% and 5-year survival rates ranging from 18to 50%. 1,39,40 A 2003 study reviewed the institutional experi-ence at Wake Forest University between 1990 and 2000. 37 Seventy-six patients were treated for acute mesenteric isch-

emia, of whom 42% had embolic disease and 58% hadthrombotic disease. Various surgical treatment options wereemployed, including exploration alone, bowel resection alone,and revascularization with or without bowel resection. Over-all perioperative mortality was 62%. When mortality wasexamined in relation to the cause of ischemia, however,patients with embolic disease tended to fare better: overallperioperative mortality was 62 to 70% for patients withthrombotic disease and 50% for those with embolic disease.None of the patients who underwent exploration alonesurvived; 33% of those who underwent intestinal resectionalone survived. In contrast to perioperative mortality, mor-bidity was higher in the embolic disease group than in thethrombotic disease group (69% versus 46%). The 5-yearsurvival rates were dismal in both groups (18%). Peritonitisand bowel necrosis at presentation were found to be indepen-dent predictors of death or survival dependent on totalparenteral nutrition.

In a 10-year institutional review from the Mayo Clinic,58 patients were treated for acute mesenteric ischemia. 1 Overall30-day mortality was 32%; however, when the data were furtheranalyzed according to the cause of ischemia, it was found thatmortality from embolic disease was 31%, mortality from throm-botic disease was 32%, and mortality from NOMI was 80%.Multiple organ failure was the most frequent cause of death.The 1-year and 3-year cumulative survival rates were 43% and32%, respectively. Independent predictors of survival includedage less than 60 years, bowel resection, and the absence of arecent major cardiovascular procedure.

Schoots and colleagues performed a systematic review ofsurvival after acute mesenteric ischemia according to underlyingcause by evaluating available data from the period between1966 and 2002. 41 The investigators examined 45 observationalstudies, which included 3,692 patients with acute mesentericischemia. They reported that mortality varied substantiallyaccording to the cause of the acute mesenteric episode. Overallsurvival was better for patients with ischemia of venous origin(i.e., MVT) than with ischemia of arterial origin. Within thecategory of arterial causes, mortality was 54.1% after treatment

Mesenteric Ischemia and Reperfusion

Although acute mesenteric ischemia is initially managedsurgically, signicant morbidity and mortality remain aftertreatment, largely resulting from local and systemic inam-

mation and the subsequent development of multiple organdysfunction syndrome (MODS). Mesenteric ischemia-reperfusion promotes local synthesis and release of variousinammatory mediators that exacerbate gut injury and primecirculating neutrophils for enhanced superoxide anion pro-duction and subsequent remote (i.e., pulmonary and hepatic)injury. 21 At the cellular level, mesenteric ischemia-reperfusionactivates a cascade of oxidative stress-sensitive protein kinasesthat converge on specic transcriptional factors to regulateexpression of proinammatory genes. These gene productsinclude enzymes (e.g., inducible nitric oxide synthase [iNOS],cyclooxygenase, and phospholipase A 2), cytokines (e.g., tumornecrosis factor– a [TNF- a ] and interleukin-1 [IL-1]), chemo-kines (e.g., IL-8), and adhesion molecules (e.g., intercellular

adhesion molecule–1 [ICAM-1]).22–28

Excessive gene activa-tion leads to a maladaptive systemic inammatory responsesyndrome that can trigger early MODS. Alternatively, thishyperinammatory state can cause local gut dysfunction,characterized by histologic evidence of mucosal injury,increased intestinal epithelial and microvascular permeability,and impaired motility; patients become more susceptibleto bacteremia and endotoxemia and, eventually, to lateMODS. 29

Experimental work suggests that mesenteric ischemia-reperfusion triggers protein phosphorylation cascades thatconverge on specic transcription factors to regulate thepattern, timing, and magnitude of expression of not only pro-inammatory but also anti-inammatory gene products. 29

Presumably, this process is mediated by alterations in thecellular redox state induced by the conversion of xanthinedehydrogenase to xanthine oxidase during ischemia, withsubsequent production of reactive oxygen metabolites andhydrogen perioxide during reperfusion. 30 Alterations in thecellular redox state activate families of stress-sensitive proteinkinases, such as the nonreceptor tyrosine kinases c-Src andSyk, PI3-kinase/Akt, and the mitogen-activated proteinkinases. These parallel kinase cascades phosphorylate nascenttranscription factors (e.g., nuclear factor– k B [NF- k B] andactivator protein-1 [AP-1]), which target genes that encodeproteins involved in mediator synthesis. 29,31

Therapies directed at attenuating these pathways havebeen successful in laboratory models of mesenteric ischemia-

reperfusion and may eventually be able to affect outcome inpatients presenting with acute intestinal ischemia. 32–36 How-ever, clinical trials investigating the efcacy of pharmacologicblockade of individual mediators (e.g., TNF- a , IL-1, andiNOS) have found this approach to be largely unsuccessfuland sometimes even deleterious in treating patients withsepsis and MODS. 32 The reasons for the failure of these trialsare probably multifactorial, but it appears that both theredundancy and breadth of the inammatory cascade andthe poor timing of therapy (i.e., the inability to target early


8/16/2019 Part06 Ch04 Copy

12/12


01/10

of arterial embolic disease, 77.4% after treatment of arterialthrombotic disease, and 72.7% after treatment of NOMI. Thedifference in mortality between embolic and thrombotic diseasemay be accounted for by the tendency of thrombosis to occurmore proximally and thus to be associated with a greater degreeof bowel infarction than that of embolic disease, and that patientswith thrombotic disease have a greater burden of underlyingcardiovascular comorbidity. A recent article highlighted theincreasing trend in the United States toward the use of endo-vascular revascularization for acute mesenteric ischemia andits potential impact on improved outcomes. 42 This studyinvestigated the outcomes of 1,857 patients who underwent

SMA percutaneous transluminal angioplasty with or withoutstenting (PTA/S) versus 3,380 patients who underwent surgi-cal revascularization from the Nationwide Inpatient Samplefrom 1988 to 2006. In-hospital mortality was signicantlyless for patients treated with PTA/S (15.6%) versus surgicalrevascularization (38.6%). Although this large retrospectivestudy certainly has inherent limitations with regard to a com-parative effectiveness analysis, novel, less invasive therapiesmay prove to be effective in reducing the tremendousmorbidity and mortality associated with this disease.

Financial Disclosures: None Reported.

References

1. Park WM, Gloviczki P, Cherry KJ Jr, et al.Contemporary management of acute mesen-teric ischemia: factors associated withsurvival. J Vasc Surg 2002;35:445.

2. Morasch MD, Ebaugh JL, Chiou AC, et al.Mesenteric venous thrombosis: a changingclinical entity. J Vasc Surg 2001;34:680.

3. Acosta-Merida MA, Marchena-Gomez J,Hemmersbach-Miller M, et al. Identicationof risk factors for perioperative mortality in

acute mesenteric ischemia. World J Surg2006;30:1579. 4. Eltarawy IG, Etman YM, Zenati M, et al.

Acute mesenteric ischemia: the importance ofearly surgical consultation. Am Surg 2009;75:212.

5. Acosta S, Milsson TK, Bjorck M. Preliminarystudy of D-dimer as a possible marker ofacute bowel ischaemia. Br J Surg 2001;88:385.

6. Akyildiz H, Akcan A, Ozturk A, et al. Thecorrelation of the D-dimer test and biphasiccomputed tomography with mesenteric com-puted tomography angiography in the diagno-sis of acute mesenteric ischemia. Am J Surg2009;197:429.

7. Ritz JP, Runkel N, Berger G, et al. [Progno-stic factors in mesenteric infarct]. ZentralblChir 1997;122:332.

8. Cikrit DF, Harris VJ, Hemmer CG, et al.Comparison of spiral CT scan and arterio-graphy for evaluation of renal and visceralarteries. Ann Vasc Surg 1996;10:109.

9. Aschoff AJ, Stuber G, Becker BW, et al. Eva-luation of acute mesenteric ischemia: accuracyof biphasic mesenteric multi-detector CTangiography. Abdom Imaging 2009;34:345.

10. Ofer A, Abadi S, Nitecki S, et al. Multidetec-tor CT angiography in the evaluation of acutemesenteric ischemia. Eur Radiol 2009;19:24.

11. Boley SJ, Kaleya RN, Brandt LJ. Mesentericvenous thrombosis. Surg Clin North Am1992;72:183.

12. Rhee RY, Gloviczki P, Mendonca CT, et al.Mesenteric venous thrombosis: still a lethaldisease in the 1990s. J Vasc Surg 1994;20:688.

13. Ernst O, Asnar V, Sergent G, et al. Compar-ing contrast-enhanced breath-hold MR angi-ography and conventional angiography in theevaluation of mesenteric circulation. AJR Am

J Roentgenol 2000;174:433.14. Demirpolat G, Oran I, Tamsel S, et al. Acute

mesenteric ischemia: endovascular therapy.Abdom Imaging 2007;32:299.

15. Wyers MC, Powell RJ, Nolan BW, et al.Retrograde mesenteric stenting duringlaparotomy for acute occlusive mesentericischemia. J Vasc Surg 2007;45:269.

16. Acosta S, Sonesson B, Resch T. Endovascu-lar therapeutic approaches for acute superior

mesenteric artery occlusion. CardiovascIntervent Radiol 2009;32:896.

17. Sommer CM, Radeleff BA. A novel approachfor percutaneous treatment of massive nonoc-clusive mesenteric ischemia: tolazoline andglycerol trinitrate as effective local vasodila-tors. Catheter Cardiovasc Intervent 2009;73:152.

18. Kaplan JL, Weintraub SL, Hunt JP, et al.Treatment of superior mesenteric and portal

vein thrombosis with direct thrombolyticinfusion via an operatively placed mesentericcatheter. Am Surg 2004;70:600.

19. Yanar H, Taviloglu K, Ertekin C, et al.Planned second-look laparoscopy in themanagement of acute mesenteric ischemia.World J Gastroenterol 2007;13:3350.

20. Thompson JS, Langnas AN, Pinch LW, et al.Surgical approach to short-bowel syndrome.Experience in a population of 160 patients.Ann Surg 1995;222:600.

21. Moore EE, Moore FA, Franciose RJ, et al.The postischemic gut serves as a primingbed for circulating neutrophils that provokemultiple organ failure. J Trauma 1994;37:881.

22. Welborn MB III, Douglas WG, AbouhamzeZ, et al. Visceral ischemia-reperfusion injurypromotes tumor necrosis factor (TNF) and

interleukin-1 (IL-1) dependent organ injuryin the mouse. Shock 1996;6:171.23. Tamion F, Richard V, Lyoumi S, et al.

Gut ischemia and mesenteric synthesis ofinammatory cytokines after hemorrhagic orendotoxic shock. Am J Physiol 1997;273:G314.

24. Panes J, Granger DN. Leukocyte–endothelialcell interactions: molecular mechanismsand implications in gastrointestinal disease.Gastroenterology 1998;114:1066.

25. Hassoun HT, Weisbrodt NW, Mercer DW,et al. Inducible nitric oxide synthase mediatesgut ischemia/reperfusion-induced ileus onlyafter severe insults. J Surg Res 2001;97:150.

26. Sonnino RE, Pigatt L, Schrama A, et al.Phospho-lipase A2 secretion during intestinalgraft ischemia. Dig Dis Sci 1997;42:972.

27. Turnage RH, Kadesky KM, Bartula L, et al.Splanchnic PGI2 release and “no reow”following intestinal reperfusion. J Surg Res1995;58:558.

28. Salzman AL. Nitric oxide in the gut. NewHoriz 1995;3:352.

29. Hassoun HT, Kone BC, Mercer DW, et al.Post-injury multiple organ failure: the role ofthe gut. Shock 2001;15:1.

30. Granger DN, Hollwarth ME, Parks DA.Ischemia-reperfusion injury: role of oxygen-derived free radicals. Acta Physiol ScandSuppl 1986;548:47.

31. Yeh KY, Yeh M, Glass J, et al. Rapid activa-tion of NF-kappaB and AP-1 and targetgene expression in postischemic rat intestine.Gastroenterology 2000;118:525.

32. Huber TS, Gaines GC, Welborn MB III, etal. Anticytokine therapies for acute inamma-tion and the systemic inammatory responsesyndrome: IL-10 and ischemia/reperfusioninjury as a new paradigm. Shock 2000;13:425.

33. Hassoun HT, Zou L, Moore FA, et al. Alpha-melanocyte-stimulating hormone protectsagainst mesenteric ischemia-reperfusion injury.Am J Physiol Gastrointest Liver Physiol2002;282:G1059.

34. Attuwaybi BO, Kozar RA, Moore-OlufemiSD, et al. Heme oxygenase-1 inductionby hemin protects against gut ischemia/reperfusion injury. J Surg Res 2004;118:53.

35. Tadros T, Traber DL, Heggers JP, et al.Effects of interleukin-1alpha administrationon intestinal ischemia and reperfusion injury,mucosal permeability, and bacterial translo-cation in burn and sepsis. Ann Surg 2003;237:101.

36. Zou L, Attuwaybi B, Kone BC. Effectsof NF-kappa B inhibition on mesentericischemia-reperfusion injury. Am J PhysiolGastrointest Liver Physiol 2003;284:G713.

37. Hassoun HT, Fischer UM, Attuwaybi BO, etal. Regional hypothermia reduces mucosalNF-kappaB and PMN priming via gut lymphduring canine mesenteric ischemia/reperfu-sion. J Surg Res 2003;115:121.

38. Hassoun HT, Miller CC 3rd, Huynh TT,et al. Cold visceral perfusion improves earlysurvival in patients with acute renal failureafter thoracoabdominal aortic aneurysmrepair. J Vasc Surg 2004;39:506.

39. Edwards MS, Cherr GS, Craven TE, et al.Acute occlusive mesenteric ischemia: surgicalmanagement and outcomes. Ann Vasc Surg2003;17:72.

40. Klempnauer J, Grothues F, Bektas H, et al.Long-term results after surgery for acutemesenteric ischemia. Surgery 1997;121:239.

41. Schoots IG, Koffeman GI, Legemate DA,et al. Systematic review of survival after acutemesenteric ischaemia according to diseaseaetiology. Br J Surg 2004;91:17.

42. Schermerhorn ML, Giles KA, Hamdan AD,et al. Mesenteric revascularization: manage-ment and outcomes in the United States,1988-2006. J Vasc Surg 2009;50:341.

Acknowledgment

Figure 4. Alice Y. Chen.


Documents

Part06 Ch04 Copy