Acute Mesenteric Ischemia Isaac George, MD Resident in Surgery Department of Surgery Columbia University College of Physicians and Surgeons Good Morning. My Standard of Care Topic this morning is Acute Mesenteric Ischemia.

Acute Mesenteric Ischemia Incidence Pathophysiology Diagnosis Therapy Treatment Algorithm Objectives One of the most difficult consults we receive are ones for acute intestinal ischemia, and that is the focus of the talk today. I will review the incidence, pathophysiology, and then move on to diagnosing and treating acute mesenteric ischemia.

Understand pathophysiology Objectives Understand pathophysiology Identify patients at high-risk for mesenteric ischemia Develop treatment plan for each patient/apply treatment algorithm The primary objectives are to understand the basic mechanisms of disease identify patients with a high likiiehood of disease And develop a treatment plan individualized for each patient

Introduction Cokkinis (1921): “occlusion of the mesenteric vessels is regarded as one of those conditions of which the diagnosis is impossible, the prognosis hopeless, and the treatment almost useless.” Occlusive or non-occlusive mechanism leading to hypoperfusion of one or more mesenteric vessels

Rationale Incidence Mortality Morbidity Recurrence 1-2/1000 hospital admissions 1% of GI admissions1 Mortality 1960’s - 70-100%2 1970’s - 60-70%3 Morbidity Cardiopulmonary, MOSF Extended LOS, TPN dependence4 Recurrence Up to 60%4 Why worry about it? TPN dependence 30% Early diagnosis improved these rates and hallmark of care of these patients Incidence likely to increase with care of older population Underestimation: subclinical disease Mortality high because diagnosis made after infarciton, gut damage proceeds even after revascularization, concomitant medcal problems and poor distal mesenteric circulation 1 Ann Surg 2001;233(6):801-808 2 Ann Surg 1982;195:554-565 3 Ann Surg 1978;188;721-731 4 Ann Vasc Surg 2003;17:72-9

Anatomic Considerations Thrombolytic review Anatomy from second image paper 70% of mesenteric blood flow-mucosa/submucosa First site of injury: transmural, mucosa to serosa Location: SB, colon

Pathophysiology: Etiology Arterial Embolic Disease Arterial Thrombotic Disease Venous Thrombotic Disease Non-occlusive Mesenteric Ischemia

Pathophysiology Arterial Embolism Majority of cases (>50%): SMA occlusion Location: origin of middle colic artery (ischemia from proximal jejunem to splenic flexure) Embolic sources: cardiac (80%)1, aortic plaques Celiac and IMA occlusion usually tolerated SMA occlusion → death Most have underlying stenoses as well 1 Ann Vasc Surg 1990;4:112-116

Arterial Thrombotic Disease Pathophysiology Arterial Thrombotic Disease 15% of acute intestinal ischemia1 Pre-existing atherosclerotic disease Worsening chronic mesenteric ischemia Found at ostium of SMA More delayed onset of symptoms 1 Vasc Surg 1996; 4th ed.

Venous Thrombotic disease Pathophysiology Venous Thrombotic disease 5-10% of intestinal ischemia Younger patient population 80% have hypercoaguable state Risk factors: oral contraceptives, previous DVT/PE, malignancy, portal HTN, nephrotic syndrome May limit arterial flow→edema, segmental infarction

Non-Occlusive disease Pathophysiology Non-Occlusive disease 20-30% of acute intestinal ischemia Response to systemic hypoperfusion Sympathetic adrenergic system mediated Visceral vasoconstriction/shunting for cerebral protection Causes: any severe systemic illness, CHF, dehydration, drugs (cocaine, ergot alkaloids, digitalis, β-blockers, α-agonist, epo), hemodialysis Can become irreversible even after cause reversed (esp in presence of atherosclerotic disease). Often stenotitc arteries present (acute on chronic disease)

Clinical Presentation: Physical Examination Arterial Thromboembolic, Non-Occlusive Severe abdominal pain Sudden onset Venous Thrombotic Less severe pain Subacute Symptoms variable Abdominal pain-non-specific, crampy vs. steady, anterior Gastric emptying/vomiting Peritonitis late Hypotension, tachycardia Acute onset of pain more common with embolus Chronic symptoms suggestive of thrombotic process

Clinical Presentation: Laboratory Limited clinical utility arterial lactate1 amylase2 CK, CK-BB3 Serum phosphate4 Other useless markers: LDH, PAF, TNF-α, AP, AST/ALT, α-glutathione Limited clinical utility due to low sensitivity, low specificity, and markers only appear after gut infarction. 1 Eur J Surg 1994;160:381-4 2 Br J Surg 1986;73:219-21 3 Dig Dis Sci 1991;36:1589-93 4 Br J Surg 1982;69:S52-3

Clinical Presentation: Risk Factors J Vasc Surg 2002;35:445-52

Clinical Presentation: Risk factors Ann Surg 2001;233(6):801-808

Clinical Presentation: Risk factors Ann Surg 2001;233(6):801-808

Clinical Presentation Ann Vasc Surg 2003;17:72-79

Clinical Presentation Ann Surg 2001;233(6):801-808

Diagnosis: Non-Invasive Imaging X-ray Computed Tomography (helical/angiography) Ultrasound MRI/MRA

Diagnosis: X-Ray Plain Films pneumatosis portal venous gas thumbprinting → Findings late, associated with high mortality AXR used to r/o other disease process (free from PUD, diverticulitis, etc)

Diagnosis: Computed Tomography Criteria pneumatosis venous gas SMA/celiac/IMA occlusion w/distal disease arterial embolism OR bowel wall thickening + one of following: lack of bowel wall enhancement solid organ infarction venous thrombosis Sensitivity: 96% Specificity: 94% Early studies: sens-64%, spec-92%1 (based on radiographic Review study from kirkpatrick 1 Radiol 2003;229:91-98

Computed Tomography Radiol 2003;229:91-98 Review study from kirkpatrick Radiol 2003;229:91-98

Computed Tomography Radiol 2003;229:91-98 Talk about advantages/disadvantages of CT Radiol 2003;229:91-98

Computed Tomography Radiol 2003;229:91-98 Talk about advantages/disadvantages of CT Radiol 2003;229:91-98

Volume Rendering: Normal Talk about advantages/disadvantages of CT RG 2002;22:161-172

Volume Rendering: Ischemia Talk about advantages/disadvantages of CT RG 2002;22:161-172

Diagnosis: Ultrasound High-grade stenosis or occlusion of SMA Sensitivity for SMA stenosis: 96% (1993) 1 Prospective, n=100 Surgically confirmed embolism/thrombus Sensitivity for SMA stenosis/occlusion: 100% (1999)2 Specificity: 98% PPV: 93%, NPV: 100% N=82, prospective Confirmed with angiography 1 J Vasc Surg 1993;17:780-788 2 Radiol 1999;211:405-410

Diagnosis: MRI Poor delineation of smaller vessels Limited clinical application Perfusion flow contrast studies show promise1 1 Radiol 2004;234:569-575

Diagnosis: Angiography Gold Standard Anatomic delineation of occlusion and collaterals Plan operative revascularization Allow infusion of therapeutic agents (lytics, vasodilators) 1 Ann Surg 2001;233(6):801-808

Principles of Treatment Diagnose Restore Flow Resect non-viable tissue Supportive Care Second-Look Difficulties of clinical trials and supporting data (review of thrombolytics)

Supportive measures Therapy IV resuscitation Optimize cardiac status Broad-spectrum antibiotics (no data) Nasogastric decompression

Therapy: Pharmacologic Anticoagulation Heparin IV Prevents clot propagation Systemic vs. intra-arterial Timing of initiation Immediately vs. 48 hr delay1,2 Restart 48 hrs after surgical intervention Warfarin Give for 6-12 mos if no clotting disorder (no data) 1 Surg Gynecol Obstet 1981;153:561-569 2 Vascular Emergencies. 1982;553-561

Therapy: Pharmacologic Vasodilators Papaverine (30-60 mg/hr) Increases cAMP, relaxes smooth muscle Primary indication: Non-occlusive arterial disease Criterion for use: Peritoneal signs absent Cannot undergo surgery Must have good distal perfusion bed Complications Continued vasoconstriction after embolus removal occurs and is prevented with papaverine

Therapy: Pharmacologic Vasodilators (cont.) Papaverine Early SMA infusion reduces mortality to 40-50%1 Directed infusion via angiography Rx: 24-48 hrs Endpoints both clinical and angiographic Subsequent surgery Complications Continued vasoconstriction after embolus removal occurs and is prevented with papaverine 1 Surg 1977;82:848-855

Therapy: Pharmacologic Thrombolysis urokinase>streptokinase, rtPA Short t½, easily reversed Dose: high vs. low 5,000 U/hr - 600,000 U/hr Direct SMA infusion vs. operative placement Have not be able to get across lesion (usually easy with acute thrombus) Am Surg 2004;70(7):600-604

Therapy: Pharmacologic Thrombolysis Duration: minutes – 48 hrs1 too long → risk of bowel necrosis Treat to re-establish flow vs. complete dissolution > 48 hrs Greater risk of bleeding Discontinue Worsening abdominal symptoms without evidence of thrombolysis Bleeding No angiographic improvement 1 JVIR 2005;16:317-329

Pooled Data No consensus on when to start, may still be a window after 18 hrs Animal data suggests that degree of stenosis more critical than duration of occlusion JVIR 2005;16:317-329

Outcomes Technical success: 43/48 Technical failure: 5/48 Outcome most dependent on age of thrombus/embolus Improvement of abd pain in 1st hour is a favorable prognostic sign Technical success does not equal clinical success Survival: 43/48 Safety No consensus on when to start, may still be a window after 18 hrs, optimal before 8-10 hrs Animal data suggests that degree of stenosis more critical than duration of occlusion Define technical failure, clinical success Technical failure not related to duration of sx, location of occlusion, agent, dose, infusion protocol Can work for total occlusion Thrombotic occlusion worse than embolic (underlying disease, distal disease) JVIR 2005;16:317-329

Therapy: Pharmacologic Thrombolysis Criterion for use: Embolic/thrombotic disease Poor operative candidates No contraindications to fibrinolytics No bowel infarction (no peritonitis/acidosis) Expansion of use to all patients without bowel infarction

Therapy: Endovascular Angioplasty/Stenting Long-term durability questioned vs. surgical repair Utility in acute ischemia setting Advantages: Shorter duration of treatment than thrombolysis Definitive treatment Based on renovascular literature, should work well with new stent technology JVIR 1999;10(7):861-867

Therapy: Endovascular Angioplasty/Stenting Ideal for thrombotic lesions Calcified ostial lesions Flow-limiting dissections Chronic occlusion Advanced techniques for embolic lesions Embolectomy w/distal protection

Therapy: Endovascular Based on renovascular literature, should work well with new stent technology J Vasc Surg 2003;38:692-8

Therapy: Endovascular Stenting Outcomes (Chronic, SMA/Celiac) 1998: Primary patency 100% at 14 mos (n=3)1 0% mortality 1999: Primary patency 74% at 18 mos (n=12)2 8.3% mortality <30 days 2003: Technical success 96% (n=26)3 Clinical success 88% Primary patency at 34 mos 65% Restenosis at 34 mos 12% 1 Cardiovasc Int Radiol 1998;21:305-313 2 JVIR 1999;10(7):861-867 3 J Vasc Surg 2003;38:692-8I

Therapy: Endovascular Stenting Indications Simple stenotic lesions Complex lesions (long-segment, irregular, heavily calcified) Total occlusion Contraindications Suspected bowel necrosis (peritonitis, acidosis, etc) diffuse distal disease Median arcuate ligament compression syndrome Balance: time for angiography vs. clinical presentation 1 J Vasc Surg 2003;38(4):692-8

Anyone with peritonitis needs to be explored. Surgery Anyone with peritonitis needs to be explored. Midline incision Evaluate extent of ischemia Doppler of entire SMA Revascularization (embolectomy vs. bypass) Re-evaluate ischemia Lastly, non-viable bowel must be resected

Surgery: Options for Revascularization Ann Vasc Surg 2003;17:72-79

Surgery: Principles Embolectomy If embolus suspected, transverse arteriotomy proximal to middle colic takeoff Embolectomy Allow reperfusion for 20-30 minutes and then re-assess bowel viability Curr Opin Cardiol 1999;14(5):453-460

Surgery: Options for Revascularization Thrombosis requires a bypass Longitudinal arteriotomy Thrombectomy Inflow adequate:  Inflow inadequate: Bypass Vein vs. graft Curr Opin Cardiol 1999;14(5):453-460

Surgery: Options for Revascularization Curr Opin Cardiol 1999;14(5):453-460

Surgery: Damage Control 24-hr second look operation Ischemia continues after acute event and reperfusion No way to determine viability initially Allows time for supportive measures to recover tissue Laparoscopy: limited in diagnostic potential-cannot exclude bowel mucosal and submucosal injury, only identifies serosal and transmural ischemia

Surgery: Options Case Reports Angiography + Laparoscopy

Outcomes After Surgery 20011 30 day mortality Embolic 59% Thrombotic 62% 20022 30 day mortality 32% 1 year mortality 57% 3 year mortality 68% 20033 Peri-op mortality 62% 20034 Peri-op mortality 15% 20055 Peri-op mortality 35% 1 Ann Surg 2001;233(6):801-808 2 J Vasc Surg 2002;35:445-52 3 Ann Vasc Surg 2003;17:72-79 4 Vasc Endovasc Surg 2003;37:245-252 5 W J Surg 2005;29:645-648

Outcomes After Surgery J Vasc Surg 2002;35:445-52

Outcomes After Surgery Ann Vasc Surg 2003;17:72-79

Outcomes TPN dependence: Significant morbidity 8-31%1,2 Significant morbidity No studies comparing stenting vs. open surgery No studies comparing embolectomy vs. bypass Early intervention most important factor for survival 1 J Vasc Surg 2002;35:445-52 2 Ann Surg 2001;233:801-808

Management of Mesenteric Vein Thrombosis 5-10% of mesenteric ischemia Subacute vs. chronic Better prognosis Diagnosis: CT scanning, venography Therapy: anticoagulation, thrombolysis surgery if bowel compromise suspected No role for venous thrombectomy Long-term anticoagulation Hypercoaguable workup 1 JVIR 2005;16:317-329 2 Surg Lap Endo Perc Tech 2003;13(3):215-217

Broad-spectrum antibiotics Hemodynamic optimization What Should You Do? Supportive IV heparin Broad-spectrum antibiotics Hemodynamic optimization Volume status Cardiac function

Other cause (perforated viscous) Supportive Measures AXR Other cause (perforated viscous) Peritonitis Yes No Not sure?? (? Laparoscopy) Suspect arterial occlusion Prompt laparotomy Open bypass vs. Angiography ± Stenting CT Angio Arterial occlusion Abdominal angiogram Venous occlusion Filling of SMA Good collaterals SMA occluded No collaterals ± Second look Thrombolysis Open bypass vs. Angiography ± Stenting Anticoagulation Anticoagulation Anticoagulation