1. 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.

2. 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.

3. 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

4. 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

5. Rationale Incidence Mortality Morbidity Recurrence
1-2/1000 hospital admissions
1% of GI admissions1
Mortality
1960’s %2
1970’s %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):
2 Ann Surg 1982;195:
3 Ann Surg 1978;188;
4 Ann Vasc Surg 2003;17:72-9

6. 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

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

8. 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:

9. 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.

10. 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

11. 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)

12. 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

13. 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:
4 Br J Surg 1982;69:S52-3

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

15. Clinical Presentation: Risk factors
Ann Surg 2001;233(6):

16. Clinical Presentation: Risk factors
Ann Surg 2001;233(6):

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

18. Clinical Presentation
Ann Surg 2001;233(6):

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

20. 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)

21. 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

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

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

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

25. Volume Rendering: Normal
Talk about advantages/disadvantages of CT
RG 2002;22:

26. Volume Rendering: Ischemia
Talk about advantages/disadvantages of CT
RG 2002;22:

27. 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:
2 Radiol 1999;211:

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

29. 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):

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

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

32. 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:
2 Vascular Emergencies. 1982;

33. 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

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

35. 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):

36. 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:

37. 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:

38. 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:

39. 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

40. 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):

41. 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

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

43. 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:
2 JVIR 1999;10(7):
3 J Vasc Surg 2003;38:692-8I

44. 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

45. 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

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

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

48. 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):

49. Surgery: Options for Revascularization
Curr Opin Cardiol 1999;14(5):

50. 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

51. Surgery: Options
Case Reports
Angiography + Laparoscopy

52. 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):
2 J Vasc Surg 2002;35:445-52
3 Ann Vasc Surg 2003;17:72-79
4 Vasc Endovasc Surg 2003;37:
5 W J Surg 2005;29:

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

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

55. 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:

56. 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:
2 Surg Lap Endo Perc Tech 2003;13(3):

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

58. 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