Ischemic disorders of the intestines

ISCHEMIC DISORDERS OF THE INTESTINES

SCOTT J. BOLEY, M.D. LAWRENOE J. BRANDT, M.D.

FRANK J. VEITH, M.D.

0011 - 3840/78/0004 - 0001505.00 O 1978 Year Book Medical Publishers, Inc.

TABLE OF CONTENTS

SELF-ASSESSMENT QUESTIONS . . . . . . . . . . . . . . 3

OBSERVATIONS ON THE PATHOPHYSIOLOGY OF INTESTINAL

ISCHEMIA . . . . . . . . . . . . . . . . . . . 6

ACUTE MESENTERIC ISCHEMIA . . . . . . . . . . . . . . 12

Cl in ica l a n d E x p e r i m e n t a l O b s e r v a t i o n s . . . . . . . . . 13

P l a n for D iagnos i s a n d T h e r a p y . . . . . . . . . . . . 22

P r i n c i p l e s of M a n a g e m e n t . . . . . . . . . . . . . . 32

R e s u l t s . . . . . . . . . . . . . . . . . . . . . 38

COLONIC ISCHEMIA . . . . . . . . . . . . . . . . . . 41

N a t u r a l H i s t o r y of Colonic I s c h e m i a . . . . . . . . . . 42

Inc idence . . . . . . . . . . . . . . . . . . . . 44

Cl in ica l C lass i f i ca t ion a n d D i s t r i b u t i o n of Colonic

I s chemic Les ions . . . . . . . . . . . . . . . . 45

E t io logy . . . . . . . . . . . . . . . . . . . . . 46

Cl in ica l F e a t u r e s . . . . . . . . . . . . . . . . . 48

D iagnos i s . . . . . . . . . . . . . . . . . . . . 48

T r e a t m e n t . . . . . . . . . . . . . . . . . . . . 55

COLONIC ISCHEMIA AND POTENTIALLY OBSTRUCTING LESIONS OF THE COLON . . . . . . . . . . . . . . . . . 57

P r o g n o s i s . . . . . . . . . . . . . . . . . . . . 59

FOCAL SEGMENTAL ISCHEMIA OF TtIE SMALL BOWEL . . . . . 59

E t io logy and P a t h o p h y s i o l o g y . . . . . . . . . . . . . 60

Cl in ica l F e a t u r e s . . . . . . . . . . . . . . . . . 61

D iagnos i s and T r e a t m e n t . . . . . . . . . . . . . . 63

CHRONIC INTESTINAL ISCHEMIA (ABDOMINAL ANGINA, INTESTINAL

ANGINA, RECURRENT MESENTERIC ISCHEMIA) . . . . . . 64

A t h e r o s c l e r o s i s of t h e Cel iac a n d M e s e n t e r i c

A r t e r i e s . . . . . . . . . . . . . . . . . . . 65

Cel iac A x i d C o m p r e s s i o n S y n d r o m e (CACS) . . . . . . . . . 74

CONCLUSIONS . . . . . . . . . . . . . . . . . . . . 81

SELF-ASSESSMENT QUESTIONS

1. What is the stimulus that causes collateral pathways to open when a major vessel is occluded?

2. To what degree may intestinal blood flow be reduced without damage to the bowel?

3. What is the effect of intestinal distention on splanchnic blood flow?

4. What is the spectrum of pathologic changes that can result from intestinal ischemia?

5. What is the present concept of the pathogenesis ofnonocclusive mesenteric ischemia?

6. What methods are available to diagnose intestinal ischemia? 7. What are the angiographic criteria for the diagnosis of mes-

enteric vasoconstriction? 8. Which patients are likely to develop acute mesenteric ische-

mia? 9. What is the purpose of the plain film in the evaluation of the

patient with possible acute mesenteric ischemia? 10. In a patient with acute abdominal pain but no abdominal

findings, what is the significance of the absence of collateral vessels when total occlusion of the superior mesenteric artery is demonstrated on an angiographic study?

11. For how long is a papaverine infusion continued when it is used in conjunction with embolectomy or arterial reconstruction?

12. When should the decision to perform a "second-look"' operation be made?

13. With the aggressive angiographic approach to the diagnosis and management of acute mesenteric ischemia, how has prognosis been altered?

14. What are the types of ulcerating colitis that occur in patients older than 50 years?

15. In the study of patients with colonic ischemia, of what value is angiography in demonstrating significant occlusion?

16. What clinical features differentiate colonic ischemia from acute mesenteric ischemia?

17. What is the role ofcorticosteroids in the management of patients with ischemic colitis?

18. By what mechanisms may obstructing lesions of the colon diminish colonic blood flow?

19. Why do the majority of patients with focal ischemia present with chronic rather than acute symptoms?

20. How well correlated with symptoms of abdominal angina is 3

the arteriographic demonstration of mesenteric atherosclerosis?

21. In which situation is reconstruction or bypass of obstructed splanchnic arteries indicated in the absence of abdominal complaints?

22. What is the present procedure of choice for arteriosclerotic occlusive or stenotic disease of the celiac axis and superior mesenteric artery?

23. What is the significance of an epigastric bruit? 24. What is the significance of angiographic demonstration of

celiac axis narrowing? 25. Does the celiac axis compression syndrome exist, and if so is

it ischemic?

Answers on Pages Shown Below

1. pp 6 - 7 10. pp. 2 8 - 2 9 19. pp. 5 9 - 6 0 2. p. 7 11. p. 31 20. p. 65 3. p. 8 12. p. 33 21. pp. 6 8 - 6 9 4. pp. 1 3 - 1 4 13. pp. 3 8 - 4 1 22. pp. 70-71 5. pp. 1 4 - 1 5 14. p. 44 23. 19. 76 6. p. 20 15. pp. 4 6 - 4 7 24. p. 76 7. pp. 2 1 - 2 2 16. pp. 4 8 - 4 9 25. pp. 7 8 - 7 9 8. pp. 2 2 - 2 3 17. pp. 5 5 - 5 6 9. pp. 2 6 - 2 7 18. pp. 5 8 - 5 9

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is Professor of Surgery at the Albert Einstein College of Medicine in New York, and Director of Pediatric Surgery at Montefiore Hospital and Medical Center. He is a grad- uate of Jefferson Medical College, Thomas Jefferson Uni- versity, and received his postgraduate training at the Jewish Hospital of Brooklyn. Dr. Boley's research interests are the mesenteric circulation and anorectal physiology, especially in relation to Hirschsprung's disease. His investigations and publications relating to these subjects date from the early 1960s, and in 1971 he edited the first book devoted solely to vascular disorders of the intestines.

is Assistant Professor of Medicine at the Albert Einstein College of Medicine and Associate Director of the Division of Gastroenterology at Montefiore Hospital and Medical Center. He received his M.D. from the State University of New York, Downstate Medical Center, and did his medical and gastroenterologic training at the Mount Sinai Hospital in New York. Dr. Brandt currently is a teaching and research scholar of the American College of Physi- cians in the field of medical nutrition and has a special interest in vascular disorders of the intestines.

is Professor and Chief of Vascular Surgery and the Trans- plant Program at Albert Einstein College of Medicine and Montefiore Hospital. He graduated from Cornell Universi- ty Medical College and did his residency training at the Peter Bent Brigham Hospital. Dr. Veith's research interests include vascular surgery as well as organ transplantation, with particular emphasis on lung transplantation.

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SINCE THE LATE 1950s VASCULAR DISORDERS of the intestine have been diagnosed with increasing frequency. This is due in part to a real increase in their incidence, but more important ly it is the result of the belated recognition of the many clinical manifestations that have as their common origin interference of normal blood flow to the bowel. This monograph is a distilla- tion of 20 years of special interest in mesenteric circulation with emphasis on our personal approach to the diagnosis and management of patients with suspected ischemia of the small or large bowel. Many laboratory investigations described in detail in our textbook on vascular disorders of the intestine, published in 1971,1 form the basis for the clinical regimens now being employed. These experimental studies can only be reviewed briefly, but their role in the evolution of our concepts will be apparent.

Although chronic intestinal ischemia was the subject of many articles in the 1960s, it has become evident that relat ively few patients suffer from this problem. Far more common are episodes of acute mesenteric ischemia with either immediate or delayed effects of the circulatory insult. The comparatively greater space devoted to acute conditions is, therefore, a reflection of their greater frequency as well as of the greater advances made in understanding their pathogenesis and improving their diagnosis and treatment. As a presentation of our personal views, this monograph makes no a t tempt to review all of the numerous con- tributions to the field of vascular disease of the intestines, but where important controversies exist they will be noted. Several extensive surveys of the recent l i terature are already available. 24 One cannot help but be impressed, however, by the accuracy of the observations of individual investigators 30, 50 and even 100 years ago, and by their perception and interpretation of the pathophysiologic consequences of intestinal ischemia. A reexamina- tion of the clinical and experimental studies done before our present sophisticated instrumentat ion was developed is both a hum- bling and exhilarating experience.

OBSERVATIONS ON THE PATHOPHYSIOLOGY OF INTESTINAL ISCHEMIA

Reduction in blood flow to the intestine may be a reflection of generalized poor perfusion as in shock or with a failing heart, or it may result from either local morphologic or functional changes. Narrowings of the major mesenteric vessels, focal atheromatous emboli, vasculitis as par t of a systemic disease or mesenteric vasoconstriction can all lead to inadequate circulation at the cellular level. However, whatever the cause, intestinal ischemia has the same end r e s u l t s - a spectrum ranging from completely reversible functional alterations to total hemorrhagic necrosis of portions or all of the bowel.

6

The intestines are protected from ischemia to a great extent by their abundant collateral circulation. Communications between the celiac, superior and inferior mesenteric beds are numerous, and a general rule that has proved valid over many years is tha t at least two of these vessels must be compromised to produce symptomatic intestinal ischemia. Moreover, occlusion of two of the three vessels occurs frequently without evidence of ischemia, and total occlusion of all three vessels in an asymptomatic pa- t ient has been observed:

Collateral pathways around occlusions of smaller arterial branches in the mesentery are provided for by the primary, secondary and tert iary arcades in the small bowel and the marginal arterial complex of Drummond in the colon. Within the bowel wall i tself there is a network of communicating submucosal vessels that can maintain the viabili ty of short segments of the intestine where extramural arterial supply has been lost.

Collateral pathways open immediately when a major vessel is occluded, in response to the fall in arterial pressure distal to the obstruction. Increased blood flow through this collateral circulation continues as long as the pressure in the vascular bed distal to the obstruction remains below the systemic pressure. If vasoconstriction develops there, it elevates the arterial pressure and this causes diminution of collateral flow. Similarly, if normal blood flow is reconstituted, the flow through collateral channels ceases.

The degree of reduction in blood flow that the bowel can toler- ate without damage is remarkable. In one of our studies, mesenteric arterial flow was reduced to 75% of normal for 12 hours. No morphologic changes could be identified by light microscopy and there was normal distribution of infused Patent Blue V dye. One reason for these findings is that only one-fifth of mesenteric capillaries are open at any one moment. Since the uptake of oxygen occurs in these open capillaries, normal diffusion of oxygen can be maintained with only 20-25% of normal blood flow. Thus, in con-

t rol led animal studies, oxygen extraction as reflected by the arteriovenous oxygen difference increased when arterial blood flow was reduced by partially occluding the superior mesenteric artery (SMA).

In the resting state the splanchnic circulation receives 28% of the cardiac output. This may increase modestly after eating or decrease during exercise, but the major changes are usually related to increased sympathetic activity. Vasomotor control of the mesenteric circulation is mediated primarily through the sympathetic nervous system. Although beta adrenergic receptors are present, alpha adrenergic receptors predominate and increased sympathetic activity produces vasoconstriction, which increases resistance and decreases blood flow. Folkow et al. 5 have shown that vasoconstriction induced by sympathetic nervous stimulation can virtually stop blood flow for brief intervals. Although

7

vasoconstriction occurs in both the arterioles and venules, the increase in precapillary resistance is relatively greater than that in postcapillary resistance, and the hydrostatic pressure within the capillary bed falls. This results in loss of plasma volume in the mesenteric bed during prolonged vasoconstriction.

Mesenteric vasoconstriction may be present and cause a reduction in blood flow, but not necessarily produce a fall to inadequate levels (ischemia). Similarly the lumen of a short segment of the SMA may be reduced by 80% with no diminution in blood flow. Moreover, intestinal ischemia can be present without intestinaI necrosis, and intestinal necrosis may be present with normal blood flow if the latter is determined after a transient episode of ischemia has been relieved. Thus, in vascular disorders of the intestines there is a frequently changing interrelationship between blood flow, the mesenteric vessels and intestinal cellular viability.

Intestinal ischemia may result from a reduction in blood flow, from redistribution of blood flow or from a combination of both. With hypotension there is decreased splanchnic blood flow as a result of vasoconstriction and arteriovenous shunting within the bowel wall2 A similar situation occurs with intestinal distention. T In both the small and large bowel, increases in intraluminal pressure over 30 mm Hg result in stepwise decreases in intestinal blood flow. However, 20-35% of control blood flow remains even at pressures of 210 mm Hg. Paralleling the fall in blood flow is a decreasing arteriovenous oxygen difference indicative of a marked diminution in oxygen extraction (Fig 1). Bowel injected with silicone rubber during distention and cleared to permit visualization of blood vessels reveals almost complete shunting away from the mucosa and muscularis propria with filling of only the submucosal and serosal arteries (Fig 2). Thus, with bowel distention there is reduction of total blood flow and redistribution away from the oxygen-consuming components of the intestine. The highly oxygenated blood flowing through the serosal arteries and veins results in a normal pink external appearance of the bowel even when total blood flow is only 20% of control. This phenomenon is reflected in the frequent clinical observation of a bowel that appears normal externally, but in which there is pronounced hemorrhagic infarction of the mucosa.

The effects of intermittent distention on both a distended segment of small bowel and the rest of the small intestine are profound, s intermittent increases in intraluminal pressure signifi- cantly reduce blood flow not only to the distended segment, but also to the entire small bowel, and this diminution in flow persists for hours after relief of distention.

The changes that occur when intestine is deprived of an adequate blood supply are both metabolic and morphologic. Brown et al., 9 using the electron microscope, noted some ultrastructural

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Fig 1.-Ef fects of bowel distention on blood flow and arteriovenous oxygen difference of intestinal blood. Oxygen extraction diminishes to almost zero as blood flow falls. (From Boley, S. J., et al.: Pathophysiologic effects of bowel distention on intestinal blood flow, Am. J. Surg. 117:228, 1969. Used by permission.)

changes within 10 minutes, and at 30 minutes found extensive changes including accumulation of fluid between cells and basement membrane. Biochemical determinations at that time showed a depression of 28% in oxygen consumption, and these investigators postulate that the mechanical separation of the cells and the basement membrane by the fluid acts as a block to modify the transport of oxygen and substrate to the epithelial cells. Thus, significant alterations in cellular function are present before any morphologic change can be detected by standard light microscopy.

The histologic changes following acute ischemia have conven- tionally been described as occurring in a sequential manner with mucosal hemorrhage progressing to mucosal necrosis with submucosal congestion, and then to submucosal hemorrhage. More severe ischemia causes deep necrosis of the submucosa and finally transmural infarction with necrosis of the muscularis propria. This concept of the progressive involvement of the layers of the bowel has been based primarily on animal experiments. Allen l~ has challenged the extrapolation of these observations to man. He demonstrated marked submucosal edema and congestion underlying intact mucosa in human intestines exposed to moderate ischemia, and believes that it is the submucosal layer that first manifests the effects of a vascular insult.

Following ischemic necrosis of the intestine, regeneration may occur and, depending on the degree of ischemic damage, total healing or varying de .grees of permanent morphologic abnormali~

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Fig 2 . -Dog intestine injected with silicone rubber. A, At normal intraluminal pressure, vessels in all four layers are filled. 13, With intraluminal pressure of 90 mm Hg, vessels in submucosa (SM) and serosa (SER) are filled, whereas those of mucosa (MUC) and muscle (MS) are a~most empty. (From Boley, S. J., et al.: Pathophysiologic effects of bowel distension on intestinal blood flow, Am. J. Surg., 117:228, 1969. Used by permission.)

10

ty may result. With involvement of the muscularis propria, fibrosis of this layer produces stenosis. When only the mucosa and submucosa are injured, complete healing can occur, but the re- generating mucosa may not be normal for weeks to months. This phenomenon explains the protracted malabsorption reported following arterial reconstruction for chronic mesenteric ischemia.

The spectrum of pathologic changes that can result from intestinal ischemia has now been demonstrated in both experimental models and in clinical studies. Depending on the severity and duration of the ischemia, its acute or chronic onset and the availability of a collateral source of blood supply, an ischemic episode can produce transient physiologic alterations, reversible morphologic changes, damaged bu t viable bowel with permanent structural defects or t ransmural infarction with gangrene and perforation. In our series of experiments with the effects of ischemia on the canine small and large intestines, we used both arterial and venous ligations and the injection of various amounts of ceramic microspheres of different diameters.l"13 The initial morphologic change following the production of ischemia was submucosal and intramural hemorrhage. This produced mucosal hil- locks that appeared as "thumbprints or pseudotumors" on bar ium enema or small bowel studies. With t ime the submucosal hemorrhage was resorbed or the overlying mucosa became necrotic and the blood was discharged into the lumen of the bowel leaving a superficial ulcer. Increasing degrees of ischemia resulted in transient superficial segmental colitis, chronic ulcerating colitis, segmental stenosis and perforation, gangrene or total liquefac- tion of the bowel. In the microsphere experiments the most pronounced damage occurred with spheres of the smallest diameter, 35/~m, which occluded vessels at a level where no collateral circulation exists. Larger spheres impacted in vessels that were proximal to the intramural collateral circulation. Other investigators have emphasized the length of the devascularized segment as the determining factor in the ult imate outcome of an ischemic episode. It is obvious that this factor is a reflection only of the length of bowel tha t the intramural collateral circulation can support and, therefore, it is bu t one of many factors that govern the bowel's response to deprivation of blood flow.

The entire spectrum of changes demonstrated in animals has now been identified clinically. The changes constitute the diverse disorders that are discussed in the following sections. Various classifications of intestinal ischemia have been proposed based on either clinical manifestations or pathologic characteristics. To enable us to develop a practical approach to the management of patients with different forms of bowel ischemia we have separated them into four broad categories, each with a general pat tern of clinical presentation that can be correlated with the nature of the

11

ischemic involvement. In three of these there is a single episode of acute ischemia, while in the fourth, chronic mesenteric ischemia, there are multiple recurrent attacks. Although, as a rule, the clinical presentation and natural h~story of each group is different, some overlap is inevitable. In such an instance, when a patient cannot be classified easily, he is managed as if he has the more serious of the conditions being considered.

The general categories are: (1) acute mesenteric i schemia- acute ischemia of major portions of the small intestine with or without involvement of the colon; (2) colonic ischemia-acute ischemia involving only the colon; (3) focal mesenteric ischemia -acu te ischemia of localized segments of small intestine; and (4) chronic mesenteric ischemia-ischemia of small and large bowel but without loss of tissue viability.

ACUTE MESENTERIC ISCHEMIA

Acute ischemia of all or major segments of the intestine supplied by the SMA has been diagnosed with increasing frequency during the past 25 years. SMA embolus, SMA thrombosis, mesenteric venous thrombosis and nonocclusive mesenteric ischemia, or the "low flow" syndrome, are the causes of this intraabdominal catastrophe, which remains as lethal today ~4, 15 as in 1933 when Hibbard et al. ~6 reported a mortality rate of 70%. The lack of improvement in the management of these vascular accidents, in spite of the advances in roentgenologic and surgical techniques to diagnose and treat them, can be attributed mainly to three factors: (1) inability to make the diagnosis before intestinal gangrene develops, (2)progression of the bowel infarction after the primary initiating vascular or systemic cause has been corrected and (3) the increasing frequency of nonocclusive mesenteric ischemia with its reported mortality rate of over 90%. 14

In 1972, we proposed an aggressive approach to the management of acute mesenteric ischemia with the hope of preventing intestinal gangrene and decreasing the extremely high mortality rate reported with this entity. ~7 The essential features in this approach are the earlier and more extensive use of angiography to diagnose mesenteric ischemia and determine its cause, and the intraarterial infusion of papaverine to interrupt the splanchnic vasoconstriction that persists after successful management of its underlying local or systemic cardiovascular cause. The proper incorporation of these concepts in a comprehensive radiologic and therapeutic plan for the management of patients with suspected acute mesenteric ischemia has resulted in an impressive improvement in both patient survival and salvage of compromised bowel.

Our approach to the management of patients with acute mes- 12

enteric ischemia is based on recent clinical and experimental observations that have provided new knowledge useful in the diagnosis and t rea tment of this entity.

CLINIOAL AND EXPERIMENTAL OBSERVATIONS

The increasing number of patients diagnosed as having acute mesenteric ischemia is reflected in our own experience at Monte- fiore Hospital and Medical Center where the incidence has risen to one per 1,000 admissions (Fig 3). This rise in the number of identified cases is undoubtedly the result of an aging population, our special interest in intestinal vascular disease and the presence of critically ill p a t i e n t s - w i t h increased risk of thrombosis, low flow states and i s chemia - in our coronary and intensive care units. Of equal importance to the increased incidence of acute mesenteric ischemia is the changing distribution of cases due to each of the different causes (Table 1).

Mesenteric venous thrombosis, cited as the most frequent cause of intestinal infarction 50 years ago, TM is responsible for only a small fraction of cases today. Much of this decline is due to the fact tha t in the past infarction in the absence of arterial occlusion was interpreted as being the result of venous thrombosis

Fig 3. - Inc idence and causes of acute mesenteric ischemia at Montefiore Hospital and Medical Center, New York, 1965-1974.

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13

TABLE 1.-CAUSES OF ACUTE MESENTERIC ISCHEMIA

S M A hIESENTERIC NONOCCLUSIVE SMA* TtIROM- VENOUS hfESENTERIC MISCEL-

EMBOLUS BOSIS THROMBOSIS ISCt IEMIA LANEOUS

Cokkinis, A. j.,8 1926 16% 2% 63%

Jackson, B. B. '" 1963 26% 24% 33%

Boley, S. J. et al. 1977 25% 8% 12%

*SMA-superior mesenteric artery.

- 19%

12% 5%

52% 3%

whi le today nonocclus ive m e s e n t e r i c i s chemia is recognized as the cause in mos t ins tances .

Mesen te r i c venous t h rombos i s can be p r i m a r y Cagnogenic" ) or secondary to a v a r i e t y of condi t ions (Table 2). Recen t ly t he r e has been a spa te of r epor t s of m i n o r and ma jo r m e s e n t e r i c venous t h romboses in pa t i en t s t a k i n g oral con t racep t ives .

Since Ende first descr ibed nonocclus ive m e s e n t e r i c i s chemia in 1958, 20 the propor t ion of m e s e n t e r i c va s cu l a r acc idents r e su l t i ng f rom th is en t i t y has r i sen f rom 12% to over 50% in our ser ies and o thers r ecen t ly repor ted . The pa thogenes i s of th i s e n t i t y is pres- en t ly be l ieved to be sp lanchn ic vasoconst r ic t ion , which occurs in r e sponse to a decrease in ca rd iac ou tpu t , hypovo lemia , dehydra - tion, vasopres so r agen t s or hypotens ion . P red i spos ing condi t ions include myoca rd i a l infarc t ion, conges t ive h e a r t fa i lure , aor t ic insufficiency, r ena l and hepa t i c d i sease or ma jo r a b d o m i n a l or card iac opera t ions . In addi t ion, a m o r e i m m e d i a t e p r ec ip i t a t i ng cause such as p u l m o n a r y edema , ca rd iac a r r h y t h m i a s or shock is

TABLE 2.-CAUSES OF MESENTERIC VENOUS THROMBOSIS

Primary Cagnogenic") Secondary

1. Hematologic and hypercoagulable states Sickle cell disease, polycythemia vera, antithrombin III deficiency, carcinomatosis

2. Local venous congestion and stasis Hepatic cirrhosis, compression of the portal venous radicles by tumor

3. Intraabdominal sepsis Cholangitis, appendicitis, diverticulitis, ulcerative colitis, peritonitis

4. Parasitic infestation Ascaris lumbricoides

5. "Low flow" states 6. Abdominal trauma 7. Iatrogenic

Abdominal operations, especially splenectomy and pancreateetomy Infusion of vasopressin into the superior mesenteric artery Oral contraceptives

14

usually present, although the intestinal ischemic episode may not become manifest until hours to days later.

Several investigators have implicated disseminated intravascular coagulation in the pathogenesis of nonocclusive mesenteric ischemia based on the presence of fibrin thrombi in intestinal specimens from patients with this entityY ~, 22 In a study of infarcted intestine from patients with occlusive and nonocclusive intestinal ischemia, we identified significant fibrin thrombi in only 20% of the intestinal sections from patients with nonocclusive mesenteric ischemia, but in 50% of those sections from patients with occlusive mesenteric ischemia. 23 Since fibrin thrombi appear to be a nonspecific feature of intestinal infarctions regardless of cause, their presence in specimens from patients with nonocclusive mesenteric ischemia should not be the basis for attributing a primary etiologic role to disseminated intravascular coagulation.

Treatment of nonocclusive mesenteric ischemia has been inef- fective in reducing its 90% mortality rate. The patients are generally elderly and extremely ill, and in the majority of cases the underlying cause of the inadequate blood flow is not amenable to surgical correction. Since many of the patients are in coronary or intensive care units, there has been an understandable reluctance in the past to subject such individuals to aggressive inva- sive diagnostic studies and therapy. However, despite their critical condition, a significant number of these patients survives major cardiac insult only to succumb to intestinal infarction. In the past, attempts to relieve the splanchnic vasoconstriction in patients with diagnosed nonocclusive mesenteric ischemia have been of questionable benefit. Local procaine blocks, epidural blocks and systemic and intraarterial phenoxybenzamine have all been used clinically. Early in our studies of the problem, we were impressed by the occurrence of nonocclusive intestinal ischemia seen at laparotomy hours to days after the primary cardiovascular problem had been alleviated. Direct procaine injections into the mesentery of the involved bowel resulted in immediate return of normal color and blood flow. This observation, together with the well-documented progression of bowel infarction after an arterial occlusion had been corrected, suggested the presence of persistent vasoconstriction and prompted an experimental investigation of this question.

The delayed or protracted effects of diminished mesenteric blood flow were studied in experiments performed on more than 200 anesthetized dogs. 24-~6 The SMA flow was decreased 50% with an hydraulic occluder and maintained at this rate while measuring alterations in cardiac output, intestinal perfusion, oxygen consumption, systemic and mesenteric arterial pressures and blood flow through other arteries of the splanchnic circulation.

The following observations are based on these studies. After a 15

50% acute diminution in SMA flow, the mesenteric arterial pressure (MAP) in the peripheral bed immediately fell by a mean of 49% (the range was 36-71%), and in several instances the percent fall in MAP exceeded the percent decrease in blood flow. While the greater fall in mesenteric pressure suggests lowered resistance or vasodilatation in the mesenteric bed, Selkurt et al. ~ have demonstrated tha t changes in active resistance cannot be deduced when pressure and flow are changing in the same direc- tion.

When SMA flow was maintained at 50%, the MAP returned to control levels within 1 - 6 hours; celiac artery flow, which had increased initially, also returned toward normal. Thus active vasoconstriction in the mesenteric bed was responsible for the return of MAP to control levels. If the occluder was released when MAP first returned to control, the SMA flow immediately rose to control levels (Fig 4) showing relief of the vasoconstriction. How- ever, if the SMA occlusion was continued for 30 minutes to four hours after MAP had returned to control levels, SMA flows re-

Fig 4.-Ef fect of low superior mesenteric artery (SMA) flow on mesenteric vascular bed. Celiac arterial flow rose and mesenteric pressure fell when SMA flow was decreased. SMA occlusion was released as soon as mesenteric arterial pressure returned to control levels, and SMA flow rose promptly to its original rate. (From Boley, S. J., et al.: Persistent vasoconstr ict ion-a major factor in non-occlusive mesenteric ischemia, Curr. Top. Surg. Res., 3:425, 1971. Used by permission.)

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Fig 5. -Effect of low superior mesenteric artery (SMA) flow on mesenteric vascular bed. Mesenteric arterial pressure returned to normal for two hours before SMA occlusion was removed, and SMA flow remained at 50% of its original flow. (From Boley, S. J., et al.: Persistent vasoconstriction-a major factor in non-occlusive mesenteric ischemia, Curr. Top. Surg. Res. 3:425, 1971. Used by permission.)

mained at 30-50% of control levels, even after removal of the occluder (Fig 5). These low SMA flows secondary to mesenteric vasoconstriction persisted and were observed for up to five hours. However, the vasoconstriction was reversed in several animals by the injection of papaverine into the SMA with an immediate return of normal SMA flow. If papaverine was infused continu- ously in the SMA (30-60 mg]hour) when SMA flow was maintained at 50%, the MAP remained down for periods up to six hours and SMA flow returned to normal promptly upon releasing the occluder (Fig 6). This demonstrated that active vasoconstriction could be prevented by papaverine.

These studies showed that low SMA flow initially produces mesenteric vascular responses that tend to maintain adequate intestinal blood flow, but if the diminished flow is prolonged, active vasoconstriction develops and may persist even after the primary cause ofmesenteric ischemia is corrected.

It has been postulated that in patients with nonocclusive mesenteric ischemia the bowel is injured during the episode ofdimin-

17

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Fig 6 . - E f f e c t of papaverine on mesenteric vasoconstriction. Papaverine was infused into the superior mesenteric artery (SMA) when SMA flow was decreased. Mesenteric arterial pressure remained down throughout the four-hour period of ischemia, and SMA flow returned to normal upon release of the occluder. Papaverine thus prevented the occurrence of vasoconstriction. (From Boley, S. J., et al.: Persistent v a s o c o n s t r i c t i o n - a major factor in non-occ lus ive mesenteric ischemia, Curr. Top. Surg. Res. 3:425, 1971. Used by permission.)

ished cardiac output or hypotension, and with correction of the primary problem, mesenteric blood flow returns to normal. This theory does not explain the operative finding of persistent ischemic bowel without venous or arterial occlusion in patients whose cardiovascular conditions have been corrected. The latter paradox can be explained, however, by our experimental observation that an episode of low mesenteric flow as brief as two hours in duration can produce mesenteric vasoconstriction that may persist for many hours after the primary problem is alleviated.

Thus, mesenteric vasoconstriction probably plays a significant role both during the acute cardiovascular episode and for varying periods after its correction. The effectiveness of locally administered vasodilators in preventing and reversing the persistent vasoconstriction following low SMA flow suggested that local intraarterial papaverine could be used clinically to treat the vasoconstriction of the low flow syndrome. Although other methods have been used to relieve this vasoconstriction, in our experience direct intraarterial papaverine injection has provided its most consistent and effective elimination.

Kukovetz and PSch 28 showed that the effectiveness of papaverine was a result of its potent inhibition of the enzyme phospho-

18

diesterase, which is necessary for the degradation of cyclic adeno- sine monophosphate (AMP) (Fig 7), the modulator of vascular smooth muscle relaxation. Drugs that stimulate the formation of cyclic AMP, e.g., prostaglandin E 1 and glucagon, have been rec- ommended either alone or in combination with papaverine to produce maximal vasodilatationY J

Laufman 3~ in 1948 furnished experimental evidence that persistent vasoconstriction also follows SMA occlusion by embolus or thrombosis. He described "residual vasospasm" in precapillary arteries after release of occlusions in the mesenteric circulation. Moreover, Martin and his associates 31 found that papaverine hydrochloride administered intravenously was of value in dilat- ing collateral vessels proximal to an arterial occlusion when they responded to the "occlusive irritant by reflex spasm." Klass '~2 and others included peripherally infused vasodilators in their treatment of arterial emboli, on the basis of relieving shock-induced vasoconstriction. However, we and others have observed prolonged vasoconstriction associated with SMA emboli that occurred in the absence of shock and persisted even after embolectomy. These clinical experiences have confirmed Laufman's experimental observations.

Furthermore, major SMA occlusions produce hypovolemia through plasma loss into the bowel, and may also result in decreased cardiac output due to myocardial depression by circulat- ing factors. This hypovolemia and decreased cardiac output in turn may also initiate splanchnic vasoconstriction. Intraarterial papaverine infused before and after the correction of an SMA occlusion for the relief of associated or persistent vasoconstriction is, therefore, a valuable adjunct to embolectomy or arterial reconstruction, as well as a primary method of treating the vasoconstriction ofnonocclusive mesenteric ischemia.

A major deterrent to treating acute mesenteric ischemia prior to intestinal infarction has been the lack of a reliable method of diagnosis. Leukocytosis, an elevated hematocrit, a metabolic acidosis with increased base deficit and white blood cells in the

Fig 7.-Concept of the role of cyclic AMP in mesenteric vascular regulation (After Jacobson).

ADENYLCYCLASE PHOSPHODIESTERASE

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STIMULATED BY: FModu,atorof ~ INHIBITED BY: J vasodilatlon J / in the / | mesenterlc | Theophylline Prostaglandln Larterlal bedJ Papaverlne Glucagon

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19

peritoneal fluid all occur with acute mesenteric ischemia, bu t are nonspecific. Elevations in the serum and peritoneal fluid levels of intestinal alkaline phosphatase are more specific but are incon- sistent findings. Increased serum phosphate levels have also been reported, but the specificity of this observation has not been established.

Several potential diagnostic radioisotope techniques have been developed in animal studies but have not been tested clinically. Schimmel et alY '~ used 99mTc pyrophosphate, which had been proved to localize in acute myocardial infarcts, but they had only moderate success in detecting intestinal infarcts by external scanning. We have also investigated the use of 99mvc col!pid sulfur-labeled leukocytes to diagnose ischemic intestine. 34 In 13 of 15 dogs, external scintigrams showed increased radionuclide uptake corresponding to the ischemic bowel. Radioactivity of the excised ischemic intestine averaged 5.9 times greater than the normal bowel. This study, which depends on the marked inflammatory response to intestinal ischemia, is of potential clinical value as it can be performed in 3 - 4 hours. In our experiments increased radionuclide uptake was detectable within two hours of the onset of ischemia and also was present 24 hours after the onset.

Another diagnostic modality that we have investigated, especially in patients who are too ill to allow for angiography, is laparoscopy. Since the intraperitoneal pressure is routinely increased by 2 0 - 3 0 mm Hg during this procedure, we studied the hemodynamic effects of such intraperitoneal pressures on the mesenteric circulation. We demonstrated profound decreases in SMA flow with pressures over 20 mm Hg, but lower pressures for brief periods produced only minimal alterations in flow. 35 We have now used laparoscopy in two patients in the period immediately following aortic operations. In both instances intestinal infarction was suspected, but the pat ient was too ill to undergo angiography. Utilizing low pressures for short periods, the intestines were visualized without any significant circulatory effects. In both patients intestinal infarction could be excluded and in one, arterial pulsations could be seen in the small bowel.

Although all of the diagnostic methods discussed can aid in the diagnosis of acute mesenteric ischemia, no one alone or in combination is definitive enough to establish the diagnosis in the absence of significant abdominal signs, which generally appear only after infarction has occurred.

Angiography has been used successfully in suspected cases of acute mesenteric ischemia, bu t until recently its role has been limited to the exclusion of an embolus or acute thrombosis, both of which might be treated successfully by prompt operation. In 1974, we reported on a series of studies '~G to establish criteria for the angiographic diagnosis ofmesenteric vasoconstriction so that

2O

nonocclusive as well as o~clusive mesenteric ischemia could be identified and intraarterial papaverine utilized to overcome the vasoconstriction.

Initially, mesenteric vasoconstriction was produced in the dog and the resulting angiographic abnormalities identified (Fig 8). Subsequently, selective superior mesenteric angiograms were examined in a control group of 65 patients to determine whether any of the observed angiographic abnormalities occurred in the absence of vasoconstriction. The reliability of these angiographic signs of vasoconstriction was then evaluated in patients acutely ill with mesenteric ischemia.

Based on these studies, four reliable angiographic criteria for the diagnosis of mesenteric vasoconstriction were identified: narrowings at the origins of multiple branches of the SMA, irregu-

Fig 8.-Experimentally induced mesenteric arterial vasoconstriction. A, base- line angiogram. B, repeat angiogram during intravenous infusion of 50 #g/min. levarterenol shows extensive vasoconstriction. C, closeup of (B) showing narrowings at origins of major branches of the superior mesenteric artery with segments of narrowing and abnormal tapering in intestinal branches. (From Siegelman, S. S., et al.: Angiographic diagnosis of mesenteric arterial vasoconstriction, Radiology 112:533, 1974. Used by permission.)

21

larities in intestinal branches, spasm of arcades and impaired filling of intramural vessels. Although mesenteric vasoconstriction occurs with hemorrhage, pancreatitis and other conditions, its presence in patients with suspected intestinal ischemia who are not in shock or receiving vasopressors is strong evidence for the presence of nonocclusive mesenteric ischemia. Thus, if angiography is performed sufficiently early in their course, patients with acute mesenteric ischemia of a nonocclusive origin, as well as those with surgically correctable occlusive lesions, can be iden- tiffed before bowel infarction occurs.

These clinical and experimental observations led us to the following conclusions:

1. The mortality rate of this catastrophe will remain at its present high level unless the diagnosis is established and therapy instituted before intestinal necrosis develops.

2. Early diagnosis can only be accomplished if all patients suspected of having acute mesenteric ischemia are given the benefit of prompt roentgenologic studies.

3. Previous reluctance to expose these severely ill patients to the rigors of angiography because of its limited value (only to exclude embolus or thrombosis) is no longer valid, as the diagnosis of occlusive and nonocclusive mesenteric ischemia is now possible and active therapeutic measures are available for both.

4. Persistent vasoconstriction probably is a major factor in both nonocclusive and occlusive mesenteric ischemia and can be relieved or prevented by direct intraarterial infusion of papaverine.

PLAN FOR DIAGNOSIS AND THERAPY

All patients suspected of having acute mesenteric ischemia are promptly treated for associated cardiovascular problems and sent for plain radiographic studies of the abdomen. Subsequent abdominal angiography is then routinely performed unless some other intraabdominal condition is diagnosed on the plain film examination. Based on the angiographic findings and the presence or absence of signs of peritoneal irritation on physical examination of the abdomen, the individual patient is then treated according to the schema outlined in Figure 9.

SELECTION OF PATIENTs,--Acute mesenteric ischemia is most likely to develop in patients over 50 years of age with either (1) valvular or arteriosclerotic heart disease, (2) long-standing congestive heart failure, especially with unsatisfactory control of digitalis therapy or prolonged use of diuretics, (3) cardiac arrhythmias of any cause, (4) hypovolemia or hypotension of any

22

origin such as burns, pancreatitis or gastrointestinal or postoperative hemorrhage or (5) recent myocardial infarctions.

Patients in any of these high-risk categories, who develop sudden onset of abdominal pain lasting more than 2 or 3 hours, are started on the management protocol (see Fig 9). Less absolute indications for an aggressive investigation are unexplained abdominal distention or gastrointestinal bleeding. These broad selection criteria are essential if early diagnosis and treatment are to be achieved, because the presence of more extensive and specific signs and symptoms usually signifies irreversible intestinal damage.

Even when the decision to operate has been made, an angiogram must be obtained to manage the patient properly. If an embolus or thrombosis is present the SMA should usually be dissected, however with nonocclusive mesenteric ischemia dissection is contraindicated. Moreover, the relief of mesenteric vasoconstriction is an integral part of our therapy for emboli and thromboses, as well as for low flow states, and can best be achieved by intraarterial infusion of papaverine through the angiography catheter.

Abdominal pain is present in 75-98% of patients with intestinal ischemia, but varies in severity, nature and location. A characteristic clinical feature is the disparity between the severity of the pain and the paucity of significant abdominal findings. Sud- den severe pain accompanied by forceful intestinal emptying is strongly suggestive of an acute occlusion. The absence of pain in up to 15-25% of patients, especially those with nonocclusive mesenteric ischemia, is the reason for including unexplained abdominal distention or gastrointestinal bleeding as relative indications for aggressive investigation in patients at risk. Disten- tion, while usually absent early in the course of mesenteric ischemia, may be the initial indication of impending intestinal infarction. Gastrointestinal bleeding may also precede any other symptom of mesenteric ischemia, and stools are positive for occult blood in up to 75% of patients.

Other symptoms and signs indicative of more advanced ischemic bowel damage, (i.e., back pain, nausea, vomiting or diarrhea) may be present when a patient is initially seen, but their presence or absence does not affect the decision to perform angiographic studies. The presence of physical signs indicating peritoneal irritation is of utmost importance, not only in selecting a patient for aggressive investigation, but in order to decide on the proper treatment. Leukocytosis, especially if out of proportion to the physical findings, an elevated hematocrit, fever and blood- tinged peritoneal fluid obtained by paracentesis are all signs of advancing intestinal necrosis but do not alter our approach to the patient; they are indications rather than contraindications for angiographic investigation.

23

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INITIAL PREPARATION AND RESUSCITATION.- Initial t rea tment is directed toward correction of predisposing or precipitating causes of the mesenteric ischemia. Relief of acute congestive heart failure, correction of cardiac arrhythmias and replacement of blood volume precede any diagnostic studies. In general, efforts at increasing intestinal blood flow will be futile if low cardiac output, hypotension or hypovolemia persist. On rare occasions we have combined dopamine administered intravenously into a peripheral vein with papaverine administered intraarterial ly into the SMA, and have been able to improve both systemic and mesenteric blood flow. Pat ients in shock should not have angiography as mesenteric vasoconstriction will always be evident even without intestinal ischemia. Such patients should not receive papaverine intraarterial ly since this will increase the size of the vascular bed and aggravate the hypovolemia. The management of congestive heart failure or shock when complicated by mesenteric ischemia is especially difficult as utilization of digitalis or vasopressors may further aggravate the diminished intestinal blood flow. Digitalis preparations all have a direct vasoconstrictor action on SMA smooth muscle, especially with the blood levels observed during rapid digitalization or with digitalis toxicity. The decision to discontinue digitalis is often difficult because the drug may be required to control rapid ventricular rates associated with atrial fibrillation or to manage severe congestive hear t failure. Vasopressors are contraindicated in the t rea tment of shock ifmesenteric ischemia is suspected.

When intestinal ischemia has progressed to the extent that systemic alterations associated with bowel infarction are present, appropriate correction of plasma volume deficits and fluid loss, gastrointestinal decompression and parenteral antibiotics are included in the preparation prior to roentgenologic studies. Mas- sive amounts of protein-rich fluid can be lost into the lumen and wall of ischemic bowel. In patients requiring large volumes of fluids a central venous or preferably pulmonary artery wedge pressure catheter is inserted to monitor rapid fluid replacement in the face of a precarious cardiac reserve.

After the initial corrective and supportive measures have been completed, roentgenographic studies are under taken irrespective of the abdominal physical findings or the surgeon's decision whether or not to operate.

PLAIN FILM STUDIES,--The initial examination includes a chest roentgenogram and roentgenograms of the abdomen with the patient in the supine, erect and both lateral decubitus positions. Signs of intestinal ischemia on plain film studies occur late and usually indicate bowel infarction. In series of cases in which a significant portion of the patients have had such signs the mortality has been dismaying. A fatal outcome occurred in 14 of 17 pa-

26

t ients reported by Frimann-Dahl, 3~ 17 of 20 patients in Hess~n's 3s series and 63 of 67 patients described by Tomchik et al. 39

A normal plain film of the abdomen does not exclude acute mesenteric ischemia, and ideally all patients should be studied before roentgenographic signs of ischemia develop. Thus, the primary purpose of these plain film studies is not to help in the diagnosis of acute mesenteric ischemia, but to exclude other radi- ographically diagnosable causes o f abdominal pain, e.g., a perforated viscus or intestinal obstruction. If no other acute abdominal condition is detected, angiography is performed.

ANGIOQRAPHY.--Emergency angiography is the keystone of our approach to acute mesenteric ischemia. Emboli, thromboses and mesenteric vasoconstriction can be diagnosed and the adequacy of the splanchnic circulation can be evaluated; the angiographic catheter also provides a route for the intraarterial administration of vasodilators.

The angiographic examination includes multiple injections of contrast material and, because most of these patients already have reduced renal blood flow, one-half the usual volume of contrast material is used in all selective studies, to reduce renal damage. An initial flush aortogram with biplane filming is obtained to detect aneurysms, dissections and emboli or other occlusions of major visceral arteries. The lat ter is important since renal or splenic arterial emboli can also present with sudden onset of abdominal pain. This pain may reflect renal or splenic infarction or intestinal ischemia due to reflex mesenteric vasoconstriction. Aortography is also used to evaluate the collateral circulation between the superior mesenteric and celiac and/or inferior mesenteric ar tery systems. A selective SMA angiogram is then performed to identify emboli, thromboses or mesenteric vasoconstriction, and to assess the perfusion of the vascular bed distal to any obstruction. If an occlusion or vasoconstriction is found, a single bolus of 25 mg tolazoline is administered into the SMA catheter followed by a repeat angiogram. This provides bet ter visualization of the peripheral circulation and indicates the potential effectiveness of a papaverine infusion. However, the response or lack of response to tolazoline does not affect the decision to use a papaverine infusion if indicated. Previously, papaverine (60 mg) was used as the bolus, bu t tolazoline has been substi tuted because of its more rapid effect. Tolazoline is not used for the infusions as it is neither as effective nor as safe as papaverine by this method of administration.

In two of our patients the abdominal pain and marked peritoneal signs resulting from mesenteric vasoconstriction disap- peared within 20 minutes after the tolazoline injection. The relief of pain and physical signs led to cancellation of scheduled lapa- rotomies, and both patients survived without operation.

27

In a normal study the major branches of the SMA, the intestinal arcades, the intramural arteries and the mesenteric veins are all visualized. Emboli typically appear as sharp rounded defects and most commonly are found just below the origin of the middle- colic artery, at the take-offpoint of the ileocolic artery, or in one of the peripheral arteries. The duration of symptoms influences the angiographic appearance of emboli. When angiography is performed immediately after the onset of abdominal pain, the emboli are apt to be sharply defined, but if the study is delayed for several days secondary thrombus may build up proximally and distally and obscure the typical configuration (Fig 10). The artery may be completely occluded, but more often the embolus only partially obstructs blood flow.

Arterial thrombosis usually occurs within 1 - 2 cm of the origin of the SMA, and almost always is superimposed on an atheromatous plaque. The SMA is totally occluded, but some filling of the artery distal to the obstruction is almost always present because

Fig lO.-Angiographic appearance of superior mesenteric artery emboli. A, recent embolus lodged at level of origin of the middle colic artery shows well- defined round contour and complete occlusion of the main artery. B, older embolus just below origin of right colic artery shows complete obstruction, but the sharp contour seen in (A) is absent. C, recent embolus at level of, and extending into, the ileocolic artery. Well-defined round edges can be seen at top and bottom of embolus.

28

Fi9 11.--Angiogram from patient with superior mesenteric artery occlusion. The prominent "meandering artery" shows that collateral channels have been present for some time and that the occlusion is not acute.

of collateral circulation. Angiographic differentiation between a thrombosis and an old embolus may be difficult; in such instances the patients are treated in i t ia l ly as if they had emboli. A more difficult problem arises when a total occlusion of the SMA is demonstrated by angiography in a patient with abdominal pain but no abdominal findings. In such an instance, it is important to be able to differentiate an acute occlusion from a longstanding one, as the lat ter may be coincidental to the present illness. The presence or absence of prominent collaterals between the superior mesenteric and the celiac and / or inferior mesenteric circulations is the decisive factor. If large collaterals are demonstrated on the angiogram, a chronic occlusion is presumed and, in the absence of any peritoneal signs, the patient is treated expectantly (Fig 11). The absence of collaterals indicates an acute occlusion, and laparotomy is indicated whether or not peritoneal signs are present.

Nonocclusive mesenteric ischemia is diagnosed when the angiographic signs ofmesenteric vasoconstriction are seen in a pa- t ient who has a clinical picture suggestive of intestinal ischemia

29

Fig 12.-Angiographic appearance of mesenteric vasoconstriction in patients. A, spasm at origins of major superior mesenteric artery (SMA) branches and multiple areas of intermittent spasm and dilatation ("string of sausages"). (Courtesy of S. S. Siegelman, Baltimore, Md) B, typical appearance of marked constriction of entire SMA and its major branches.

but who is neither in shock nor receiving vasopressors. The angiographic findings may vary from localized spasm to a "pruned" appearance of the entire mesenteric arterial tree (Fig 12).

Angiographic studies in patients with mesenterie venous thrombosis may be normal especially if only segmental veins are involved. To our knowledge, the angiographic diagnosis of mesenteric venous thrombosis has not been made clinically, but based on experimental studies ~~ angiographic findings may include: (1) spasam of the SMA and its major branches; (2) prolongation of the arterial phase; (3) intense opacification of the bowel wall; (4)failure to opacify the mesenteric and portal veins.

T H E R A P E U T I C P A P A V E R I N E I N F U S I O N . - - When the therapeutic re- gimen includes the use ofpapaverine, the drug is infused through the angiography catheter, which is left in the SMA. To prevent dislodgment, the catheter is sutured to the skin at its point of en- try in the thigh. The papaverine is administered at a constant rate of 30-60 mg/hour using an infusion pump. It is usually di- luted in saline to a concentration of 1.0 mg/ml, but this may be varied with the fluid limitations or requirements of the patient. Continuous monitoring of systemic arterial pressure and cardiac rate and rhythm is indicated as these amounts of papaverine theoretically could have systemic effects. We have not observed such problems in either our experimental or clinical studies probably because the drug is metabolized in the liver before it reaches the general circulation. Infusion at these rates has been used clinically for as long as five days without untoward systemic changes.

Heparin is not added to the infusion as it is not compatible with papaverine hydrochloride and we have not found it necessary to

3O

prevent thrombus formation within the SMA. No other medica- tions or fluids should be administered through the arterial catheter, and the patient must be observed carefully for evidence of dis- lodgement of the catheter.

The duration of the papaverine infusion varies both with the purpose for its use and the response of the patient. In conjunction with embolectomy or arterial reconstruction, the infusion is continued for 12-24 hours if no "second look" is planned. At that time the angiogram is repeated and, unless some specific indication for more prolonged vasodilator therapy is demonstrated the infusion'is discontinued. When a second look operation is to be performed, the papaverine is continued until the abdomen is reo- pened, but a repeat angiogram is obtained prior to operation. The need for an additional period of infusion is assessed intraopera- tively, depending on the state of the bowel and the results of the preoperative angiogram.

When papaverine infusion is used as the primary treatment for nonocclusive mesenteric ischemia, it is continued for approximately 24 hours and then a repeat angiogram is performed 30 minutes after changing the infusion to isotonic saline without papaverine. Based on the clinical course of the patient (i.e., abdominal distention, bowel function, abdominal findings and evi-

Fig 13.-Patient with nonocclusive mesenteric ischemia managed with papaverine infusion for three days. A, initial angiogram showing spasm of main superior mesenteric artery, origins of branches and intestinal arcades. B, angiogram after 36 hours of papaverine infusion. Study was obtained 30 minutes after papaverine was replaced with saline. At this time the patient's abdominal symptoms and signs were gone.

31

dence of blood in the stools), and the response of the vasoconstriction to therapy as noted on the angiogram, the infusion is discontinued or maintained for another 24 hours; the patient is then reevaluated (Fig 13). Infusions have been continued for up to five days, but usually can be stopped after 24 hours. When papaverine is used in conjunction with laparotomy for nonocclusive disease, a second look is frequently necessary. In such cases the infusion is continued as described previously for second look operations following embolectomy. The papaverine infusion is discontinued when no signs of vasoconstriction remain on an angiogram that ig obtained 30 minutes after the vasodilator infusion is temporarily replaced by saline alone. The SMA catheter is removed promptly when the intraarterial infusion is stopped.

SUPPORTIVE THERAPY.--An essential aspect of the supportive therapy of patients with acute mesenteric ischemia is the mainte- nance of an adequate plasma volume. Jus t as massive losses of protein-rich fluids occur with early bowel infarction, so may they occur following revascularization of ischemic bowel. Hence, it is important to continually correct for losses before undertaking treatment, during papaverine infusions and following surgical relief of arterial occlusions. The use of low-molecular-weight dex- t ran may serve a dual purpose because of its effect as a plasma expander and because of its potential value in decreasing sludg- ing in the microcirculation.

The value of both systemic and locally administered antibiotics in improving the viability of compromised bowel is well accepted. For this reason, and because of the high incidence of positive blood cultures with acute mesenteric ischemia, systemic antibiotics are started as soon as the diagnosis is established. Antibiotics can also be locally instilled into the intestine by means of a fine catheter inserted at the time of operation, as described by Delany et al. 4~

Intestinal decompression by nasogastric suction, the use offu- rosemide and mannitol to mainta in ur inary output, and specific therapy for the cardiac problems all play a role in the management of most patients. Digitalis, as previously mentioned, must be used cautiously, and vasopressors should be avoided. Anticoag- ulant therapy is specifically avoided except in venous thrombosis because of the danger of intestinal hemorrhage. Early in our experience we had two patients who bled massively as a result of heparin administered after successful embolectomy.

PRINCIPLES OF MANAGEMENT

Laparotomy is indicated during the course of acute mesenteric ischemia either to restore intestinal arterial flow, i.e., after an embolus or thrombosis, or to resect irreparably damaged bowel. A

32

long midline incision or another equally adequate incision is used to permit a complete assessment of the intestine and its blood supply. Embolectomy or arterial reconstruction precedes any evaluation of intestinal viability; bowel that initially appears infarcted may show surprising recovery. After completion of any required arterial surgery the entire gastrointestinal tract is examined, as there may be patchy necrosis with no discernible pattern. This is particularly common with low flow states. It is our policy to resect just the frankly necrotic bowel at the initial laparotomy and to perform a primary anastomosis, except when only a short segment of intestine is involved. There is no reliable objective means for determining the viability of ischemic intestine. Mea- surements of serosal temperature and pH, electromyography, the distribution of injected vital dyes or 99mTc-tagged albumin microspheres and direct Doppler determination of serosal blood flow are the experimental methods that are being evaluated. Clinical assessment of the color of the bowel, and the presence of pulsations, bleeding and peristalsis remain the inexact criteria upon which this judgment is made. If there is any question of the viability of any remaining intestine, a planned reexploration, or second look, is performed within 18-48 hours. A second look procedure is not routinely done if the intestine appears arterialized adequately. Thrombosis at the site of embolectomy or arterial reconstruction, which occurs fairly commonly, is excluded by the angiogram performed through the infusion catheter 24 hours after operation.

If the viability of the bowel is doubtful at the initial laparotomy, a plastic catheter is inserted in the proximal jejunum by the needle technique to permit instillation of antibiotics while await- ing reexploration.

THE e~SECOND LOOK". -- The decision to perform a second look is made at the initial laparotomy if there is questionable viability of either a major portion or multiple segments of intestine. If a single, limited portion of bowel is involved, it is better to resect this at the primary procedure. The purpose of the second look, as proposed by Shaw, is ~'not just to allow a clear definition between dead and live bowel to take place, but also to allow time for the institution of supportive measures, which may render more of the bowel viable. ''4~

This concept is especially applicable to our therapeutic plan, since the use of papaverine infusions in the postoperative period is precisely the type of measure Shaw had in mind in his original proposal. The infusion catheter also allows for a repeat angiogram, which may be helpful in the planning of the secondary procedure. The use of this and other supportive measures previously described is essential in the interval between operations if the state of the ischemic bowel is to be improved.

33

Two basic tenets of the second look are that (1) the decision to perform it is made at the inital laparotomy and (2) once decided upon it is performed regardless of the patient's condition. The reexploration is generally performed between 18 and 48 hours after the primary operation, but deterioration of the patient's condition may signify the need for earlier intervention.

ARTERIAL EMBOLUS.-Emboli to the SMA most commonly lodge at the level of the middle colic artery (55%), but they can occlude the entire SMA at its Origin (18%) or lodge in the vicinity ofthe~ right colic artery (16%) or the ileocolic artery (7%). ~9 As a rule all patients with emboli in the SMA proximal to the origin of the ileocolic artery are operated on whether or not peritoneal signs are present. With more peripheral emboli, a laparotomy is performed only if abdominal findings persist 30 minutes after the tolazoline injection. All patients with emboli, excluding those with minor emboli in peripheral jejunal or ileal arteries, are begun on a pao paverine infusion immediately after the angiogram. This is continued during and after the operation in patients undergoing embolectomy, and for at least 24 hours in patients being observed with minor emboli.

If occlusion of the SMA is demonstrated on the angiogram but its cause cannot be determined (i.e., embolus or thrombosis), the obstruction is initially approached surgically as if it were an embolus. However, in any patient with an acute mesenteric occlusion, the groin and thigh should be prepared and draped within the field so that a segment ofsaphenous vein may be obtained for arterial reconstruction.

As previously stated, the embolectomy is performed before making any assessment of the viability of the intestines. We prefer to approach the embolus directly, or through a proximal arteriotomy, rather than through a peripheral branch as has been suggested~, 43. The proximal SMA is approached by drawing the transverse colon superiorly and anteriorly, and packing off the small intestine inferiorly. The inferior leaf of the transverse mesocolon is incised and the proximal SMA is identified by dissection between the pancreas and duodenum. The origin of the middle colic artery is identified and isolated at this point, and the main vessel freed for a distance of 2 -3 cm proximal and distal to the origin of this branch. After identifying the site of embolic occlusion, the vessel is occluded proximally and distally with double-looped tapes, gentle vascular clamps or bulldog clamps (Fig 14, A). A longitudinal arteriotomy is made over the embolus or just proximal to it. We favor placement of the arteriotomy in the SMA above the origin of the middle colic artery because the larger diameter at this level lessens the chance of narrowing at the site of closure. The embolus is removed and the proximal and distal occlusions released to flush out retained fragments of clots.

34

<.._

-- c /

"4/.,#, J I Fig 14.-Technique of superior mesenteric artery embolectomy. A, the artery

has been isolated at the base of the transverse mesocolon and controlled with tapes. B, longitudinal arteriotomy placed proximal to the origin of the middle colic artery. A Fogarty catheter has been passed distally. C, the arteriotomy closure using a vein patch. The patch is usually not required. (From Boley, S. J., et al.: An aggressive roentgenologic and surgical approach to acute mesenteric ischemia, in Nyhus, L. M. (ed.): Surgery Annual [New York, Appleton- Century-Crofts, 1973.] Used by permission.)

A Fogarty balloon catheter is then passed proximally and distally to further assure removal of all residual clots (Fig 14, B). The arteriotomy is closed with or without a vein patch using fine vascular suture technique (Fig 14, C).

Following embolectomy, if no second look is planned, the papaverine infusion is continued for 12-24 hours, and an angiogram is obtained immediately prior to removing the catheter. When a second look is scheduled the infusion is maintained until that procedure is completed.

Although we cannot recommend it at present, we have managed three patients with major emboli using intraarterial papaverine infusions as the primary form of therapy. Operation was temporarily interdicted in all, and after a trial of vasodilator therapy intestinal perfusion appeared adequate on the angiogram. In all three, the bowel remained viable without embolectomy. This was determined at laparotomy in two patients; the third survived without operation. The role of this nonoperative therapy for SMA embolus remains to be defined. However, some support for the concept is provided by our most recent animal experiments, demonstrating that intraarterial papaverine increases

3 5

the survival of dogs subjected to six hours of SMA occlusion. Fur- ther investigations of the efficacy of a combination of intraarterial papaverine and a thrombolytic agent are in progress.

A C U T E M E S E N T E R I C ARTERY THROMBOSIS. - - A n acute SMA thrombosis is diagnosed by the presence of a total SMA occlusion without enlarged collateral vessels. Operation is always indicated. If the position of the angiographic catheter permits, a papaverine infusion is started preoperatively and maintained during the arterial reconstruction.

Although it is possible to perform a thromboendarterectomy on the SMA at its origin, this may be difficult, particularly in obese patients. We generally favor the use of an aorta-to-SMA bypass using a segment ofsaphenous vein24 The insertion of the vein is made on the SMA at or distal to the origin of the middle colic branch (Fig 15). With more distal thromboses, which are relatively rare, thromboendarterectomy can be performed with much

Fig 15.-Technique of aorta-to-superior mesenteric artery (SMA) bypass. An incision in the retroperitoneum has been made over the aorta and carried superiorly to divide the ligament of Treitz. This provides exposure of the aorta and the SMA in the region of the middle colic artery. Sites of the anastomoses are shown. Inset left shows fine suture technique of anastomosis. Inset right shows completed bypass.

36

less difficulty than with those at the origin of the SMA. However, these too can be managed by a graft placed between the aorta and the SMA distal to the obstruction. An alternative approach is to anastomose the ileocolic terminal branch of the SMA to the subja- cent right common iliac artery, either end-to-side or side-to-side. The small caliber of the ileocolic artery, however, might make this a more difficult procedure with an anastomosis that has a lesser chance of remaining patent.

NONOCCLUSIVE MESENTERIC ISCHEMIA. - - A papaverine infusion is begun on all patients with nonocclusive mesenteric ischemia as soon as the diagnosis is made,-and in patients with persistent peritoneal signs the infusion is continued during and after laparotomy. The method for determining when to terminate the papaverine infusion has,already been described.

At operation manipulation of the SMA is kept to a minimum. Obviously necrotic bowel is resected and a primary anastomosis performed. If bowel of questionable viability is left behind, a second look is scheduled. It is better to leave bowel of doubtful viability than to perform a massive small bowel resection, for in many instances the circulation will have improved by the time of the second exploration.

ACUTE MESENTERIC VENOUS THROMBOSIS. - -Mesenter icvenous thrombosis is most often diagnosed at laparotomy since angiography is usually normal and the patient is explored because of the presence of peritoneal signs. The thrombosis may involve the superior mesenteric vein (SMV) and portal vein, but more frequently involves a segmental jejunal or ileal vein. As previously discussed, mesenteric venous thrombosis may be primary or secondary. However, regardless of etiology, the operative management is the same. During the operation the diagnosis can be confirmed by mesenteric venous angiography and pressure measurements performed through a peripheral venous branch.

Localized intestinal infarcts are resected and primary anastomoses performed. When most of the small bowel is involved but not frankly infarcted, a thrombectomy should be attempted. If thrombosis of the SMV and/or portal vein is identified, the SMV is dissected out just below the pancreas and proximal and distal control obtained. Through a transverse venotomy in the SMV, a Fogarty catheter is passed up to the liver and clot from the portal vein removed. Clot from the intestinal side of the venotomy is removed by pressure on the intestines and mesentery and by passage of a small Fogarty catheter distally. Good blood flow must be obtained from both the portal and peripheral ends of the venotomy. The venotomy is closed with simple interrupted sutures without a patch graft25

Mesenteric venous thrombosis is the one condition in which 37

an t icoagu lan t s are used rou t ine ly pos topera t ive ly a f t e r bo th resec t ion and th rombec tomy. H e p a r i n and t h en Coumadin a re admin i s t e red to p r e v e n t the f r equen t r ecur rence of venous th romboses.

RESULTS

This aggress ive approach to pa t i en t s wi th suspected acute mesen te r i c i schemia has been adopted because of t h e d isas t rous resu l t s we and o the r s have had wi th more expec t an t m e a n s o'f d iagnosis and the rapy . Mor ta l i t i es of 7 0 - 9 0 % for th is condi t ion have been repor ted t h r o u g h 1977. We have recen t ly repor ted our resu l t s wi th the first 50 pa t i en t s in the group "a t r i sk" who developed pers i s t en t abdomina l pa in and were m a n a g e d by the approach described. ~6

T h e y r anged in age from 51 to 88 years ; 27 pa t i en t s were over 70 years . Associated compl ica t ing condit ions are l is ted in Table 3. While the aggress ive approach is ideal ly begun wi th in 3 - 4 hours of the onse t of abdomina l pain, in t e rva l s of severa l hours to days occurred in more t h a n ha l f the pa t ients . These resu l ted f rom both

TABLE 3.-ASSOCIATED COMPLICATING CONDITIONS IN 50 PATIENTS WITH SUSPECTED ACUTE

MESENTERIC ISCHEMIA

NO. OF PATIENTS

Congestive heart failure 23 Cardiac arrhythmia 22 Hypotension 6 Respiratory failure 4 Sepsis 3 Renal failure 2

TABLE 4.-DIAGNOSES IN 15 PATIENTS WITHOUT ACUTE MESENTERIC ISCHEMIA

NO, OF DIAGNOSIS MADE ON PATIENTS ANGIOGRAPHIC STUDY

Carcinoma of the colon 3 Ischemia of the colon 2 Small bowel obstruction 1 Ruptured aortic aneurysm 1 Splenic artery embolus 1 Renal artery embolus 1 Diverticulitis 1 Perforated appendicitis 1 Diabetes mellitus 1 Cause of abdominal pain undetermined 3

15

2 2 1 1 1 1 0 0 0 0 8

38

TABLE 5.--RESULTS OF AGGRESSIVE APPROACH IN 35 PATIENTS WITH ACUTE MESENTERIC ISCHEMIA

NO. OF DIAGNOSIS PATIENTS ALIVE DEAD MORTALITY

Nonocclusive mesenteric ischemia 40% No peri toneal signs 5 5 0 Peri toneal signs 10 4 6

SMAt Embolus 56% No peri toneal signs 4 3 1 Peri toneal signs 12 4 8

SMA thrombosis 33% No peri toneal signs 2 2 0 Peri toneal signs 1 0 1

SMV$ thrombosis 0% No peri toneal signs 0 0 0 Peri toneal signs 1 1 0

Total 35 19" 16 46%

*Seventeen of 19 survivors re ta ined all or most of the i r bowel. tSMA = superior mesenteric artery. $SMV = superior mesenter ic vein.

patient delays in seeking medical attention and from physician delays in undertaking the necessary steps for early diagnosis and treatment.

Of the 50 patients studied, 35 (70%) proved to have acute mesenteric ischemia. Thirty-three had angiographic signs of nonocclusive or occlusive ischemia. The other two patients had normal angiograms. One of these had gangrenous colon at operation but subsequently developed infarction of most of his small bowel; the other had a localized venous thrombosis. Fifteen of the 50 patients (30%) did not have mesenteric ischemia, but in 8 of these 15 the correct diagnosis was made from the angiographic study (Table 4).

The diagnosis and outcome in the 35 patients with acute mesenteric ischemia are shown in Table 5. The overall mortality was 46%. Nine of the 10 patients without peritoneal signs at the time of angiography survived, while only 10 of 25 with peritoneal signs survived.

Seventeen of the 19 surviving patients required no intestinal resection or had removal of less than 3 ft. of bowel.

NONOCCLUSIVE MESENTERIC ISCHEMIA (15 PATIENTS). I F i v e patients had no peritoneal signs and all survived without operation. Seven of the 10 patients with peritoneal signs were operated on and all had gangrenous bowel. In two of these the involvement was too extensive for resection. The five others underwent resection and two survived. Three patients with peritoneal signs were not operated on. One died before an operation could be performed, and in the other two the pain and abdominal findings subsided after a vasodilator was infused into the SMA.

39

SMA EMBOLUS (16 PATIENTS). -- In all but one of the 16 patients the embolus involved the main SMA at or above the ileoco- lie branch. The remaining patient had small emboli present in ileal and jejunal arteries. Seven of the 16 patients with SMA emboli also had emboli in arteries other than those of the mesenterie circulation.

Thirteen patients with SMA emboli were operated on. Embo- lectomy alone was performed in six, embolectomy and bowel resection in three and resection alone in two. In two patients, only a laparotomy was done; in one the bowel was completely normal after 54 hours ofpapaverine infusion, and in the other the extent of the infarction precluded resection. Of the three patients not operated on, one died before operation could be performed, one refused operation but survived and one had small emboli in the ileal and jejunal branches. The latter patient was not operated on for his SMA emboli but succumbed to complications ofem- boli elsewhere.

Two patients developed short segments of ischemic enteritis after embolectomy. In one of these the enteritis was transient and healed in several weeks, but in the other persistent diarrhea and severe protein loss necessitated resection of the involved bowel.

Three patients were managed initially with papaverine infusions for 24, 36 and 54 hours, respectively. Two were subsequently operated on and the bowel was found to be normal. The third survived without operation.

THROMBOSIS (4 PATIENTS).--TwO of the three patients with SMA thrombosis survived, one after thrombectomy and one after bypass. The third had extensive gangrene of the bowel. The one patient with venous thrombosis survived after segmental small bowel resection.

COMPLICATIONS.--Three patients developed transient acute tubular necrosis following angiography and treatment of their mesenteric ischemia. One patient developed arterial occlusions in both lower extremities during a papaverine infusion for an SMA embolus. These probably represented other emboli from his primary source of embolization, but the SMA catheter could not be excluded as a factor. There were several instances of local hema- tomas at the arterial puncture site, but no other major problems were encountered with blood flow to the lower extremities.

Problems with prolonged papaverine infusions have been mini- ma]. Infusions for more than five days have been used without significant systemic effects. More than 90% of the drug is inacti- vated with each circulation through the liver so large doses can be given safely into the mesenteric circulation. Fibrin clots on the arterial catheter have been observed commonly, but have not caused any difficulty. Three catheters clotted and had to be removed, but this complication can be avoided if a continuous infu-

40

sion pump is used. Catheter dislodgment occurred several times and required replacement under fluoroscopy.

The 54% survival rate in the present series when compared with the 20-30% survival previously reported is encouraging. Equally gratifying is the preservation of a normally functioning gastrointestinal tract in 85% of the surviving patients.

The survival of 9 of the 10 patients with acute mesenteric ischemia who had angiography in the absence of physical signs of peritonitis demonstrates the potential value of early diagnosis. ~ Ideally all patients with acute mesenteric ischemia should be studied before physical signs develop, at a time when the plain films of the abdomen are normal. Physical signs and plain film abnormalities usually indicate the presence of bowel necrosis. Therefore, to wait for these to develop is to wait for ischemia to progress to infarction and to accept the high mortality that ac- companies this progression.

Despite our encouraging initial results with this approach there have been several disappointing aspects of our experience. One is the long delay before angiography in so many of the patients. The second is that during the period of this study an equal number of patients with acute mesenteric ischemia were seen at our center but were not managed according to protocol, despite avid interest in this problem by the departments of medicine, radiology and surgery. Factors contributing to these problems were (1) the reluctance of internists to use angiography in the absence of abdominal findings or radiologic evidence ofischemic bowel, (2) the difficulties in obtaining immediate emergency angiography a ta l l times of the day and night and (3) the impatience of surgeons who felt compelled to operate without obtaining an angiogram.

The aggressive approach to acute mesenteric ischemia offers promise of a markedly improved prognosis for patients with these vascular catastrophies. We believe that the results of earlier application of the diagnostic and therapeutic methods included in this approach justify the risks and will ultimately increase both the number of survivors and the quality of their survival. An increased awareness and acceptance of the need for early angiographic study in patients at risk must be the first step in wider adoption of these concepts.

COLONIC ISCHEMIA

In our experience, ischemia of the colon is presently the commonest vascular disorder of the intestines. However, prior to the late 1950s most reports of intestinal vascular disease were related to catastrophic mesenteric vascular accidents involving the small, and only rarely, the large intestine. In the 1950s the increasing number of operations for aortic aneurysm and the

41

introduction of ligation of the inferior mesenteric artery (IMA) during resections of colonic carcinoma resulted in numerous instances of large bowel ischemia with gangrene, stricture and colitis.A7, 4s Experimental and clinical studies during the past .15 years have led to the recognition of both the full gamut of pathologic changes produced by intestinal ischemia and the protean clinical manifestations with which it may be present. In 1963, based on a series of laboratory and clinical investigations, Boley, Schwartz and their co-workers first identified the spontaneous and reversible nature of some episodes of colonic ischemia, and described the radiologic criteria for their early diagnosis.", ,2 The ability to diagnose colonic ischemia in its early stages en- abled those investigators to observe the natural history and late results of acute ischemic insults, and led to their emphasis of the vascular origin of segmental colitis in the aged, nonspecific colonic ulcers and colonic strictures.", ,2.4,J

As is often the case when conditions are first described, many names have been applied to the various clinical forms of colonic ischemia. While each term characterizes one aspect of the condition, their multiplicity and the overlapping of the pathologic changes they signify have tended to confuse rather than clarify the problem. Moreover, with increased knowledge some names appear to be inaccurate. Thus, our original description of "reversible vascular occlusion of the colon"" is incorrect in that there may be no demonstrable occlusion responsible for the ischemia, and it is the effect, rather than the occlusion, which is reversible. Similarly, the terms "ischemic colitis T M and "colonic infarction" are not entirely suitable, for the milder reversible ischemic episodes are not inflammatory but hemorrhagic, and coagulation necrosis (infarction by definition) is often absent. An appropriate overall designation is colonic ischemia, which can be applied to both reversible and irreversible lesions. Specific forms ofischemic damage can then be identified pathologically and clinically as: (1) reversible ischemic lesions of the colon or reversible ischemic col- opathy; (2) reversible or transient ischemic colitis; (3) chronic ischemic colitis; (4) ischemic colonic stricture; or (5) ischemic colonic gangrene. By thus eliminating nonspecific terminology, the experience of many clinicians can be combined and uniformly compared so as to broaden our understanding of these entities.

NATURAL HISTORY OF COLONIC ISCHEMIA

We have previously emphasized that regardless of its cause bowel iscehmia produces a single spectrum of pathologic, clinical and radiologic manifestations. The effects of individual episodes of colonic ischemia fall within this pattern and vary with the severity of the ischemic period. The pathologic changes evoked by ischemia have already been described in detail. In summary, they

42

/ ROENTGENOLOGIC / AND

CLINICAL HEALING

RATION

IRREVERSIBLE DAMAGE--SEGMENTAL COLITIS

~STRICIURE Fig 16.-Various end results of colonic ischemia.

range from simple submucosal edema at one extreme to infarction and necrosis at the other. Between these are gradations of tissue damage, which form the basis for the diverse clinical courses that colonic ischemia may take (Fig 16). Mild ischemia produces morphologic changes that will regress and ul t imately disappear or heal, a sequence of events that is reflected clinically and radiologically by transient, or reversible, colonic findings. More severe ischemia may result in irreparable damage with gangrene, perforation or persistent colitis; if healing occurs it does so with scarring, fibrosis and resul tant stricture.

The ul t imate outcome of an episode of colonic ischemia depends on many factors. Among these are (1) the cause, i.e., occlusion or low flow; (2) the caliber of the occluded vessel; (3) the duration and degree of the ischemia; (4) the rapidity of onset of the ischemic process; (5) the adequacy and efficiency of the collateral circulation; (6) the state of the general circulation; (7) the metabolic requirements of the affected bowel; (8) the presence of bacteria within the lumen; and (9) the presence of associated conditions, such as colonic distention. Although the end results of the inter- action of all of these factors are obviously multifold, the initial response to ischemia may be the same regardless of its severity. It is, therefore, impossible to predict the progression of the ischemic process from the initial physical, radiologic or sigmoidoscopic evaluation. Furthermore, several months may be required for healing or cicatrization of an involved segment of colon, so that the final classification of a lesion cannot be made until either complete healing occurs or a nonreversible lesion is demonstrated or excised.

43

INCIDENCE

An accurate determination of the incidence of colonic ischemia is impossible because the various clinical manifestations of the disorder have only recently been recognized. Also, unless bar ium enemas are performed early, many cases of transient, or reversible, ischemic lesions will be missed. However, in centers with a special interes~ in intestinal vascular disease ischemic lesions of the colon appear to be more common than those of the small bowel. This observation is supported by the more than 150 cases that form the basis of our experience, as well as the numerous other cases reported since our original paper in 1963. Previous reports stressing the greater frequency of small intestinal lesions, i.e., Frimann-Dah137 and Laufman and Scheinberg, 51 were based on the number of acute occlusions of the SMA as compared to those of the IMA, and did not reflect the noncatastrophic cases that make up the majority of ischemic lesions of the colon. When we first described the reversible and spontaneous forms of colonic ischemia, the usual question posed was, ~'Why haven' t we seen these cases before?" A fundamental reason was the failure to ob- tain barium contrast studies of the bowel early in the course of the disease, but of equal importance was simple lack of recognition. Thus, retrospective studies of clinical material have yielded many previously undiagnosed cases, and similarly a review of the l i terature reveals early descriptions that in retrospect are obvious cases of colonic ischemia.

An example of a retrospective study is Wright's review of a series of patients who developed ulcerating colitis after the age of 50 years. 52 After reviewing the .clinical, radiographic and pathologic findings, Wright classified one-half of these cases as definite ischemic colitis, one-quarter as probably ischemic colitis and only one-quarter as idiopathic ulcerative colitis. No patient was considered to have Crohn's disease. Typical of older reports in which the etiologic importance of ischemia was not recognized are those of Boreham and Kellock. Boreham described six patients with "benign strictures of the colon", ~3 which clinically and radiologically are characteristic ischemic strictures. The eight patients with acute segmental ulcerative colitis reported by Kellock ~4 include excellent examples of reversible ischemic lesions. With increased awareness by clinicians and radiologists, and the emphasis on the performance of barium enemas early in the evaluation of patients with rectal bleeding, colonic ischemia is being recognized as one of the more common colonic disorders.

Of 150 cases of colonic ischemia (in 148 patients), 53% occurred in females and 47% in males. Although the patients ranged in age from 1 to 87 years, 91% of those whose lesions were not iatrogenic were in the seventh decade or older. This prevalence in the

44

older age g roup is conf i rmed by o the r r epor t s and is to be expected in v iew of the de t e r io ra t ion of the v a s c u l a r t ree t h a t occurs w i th aging,

CLINICAL CLASSIFICATION AND DISTRIBUTION OF COLONIC ISCHEMIC LESIONS

The majority of episodes of colonic ischemia produce transient reversible changes, especially when the ischemia is not iatrogenic in origin. The nature and severity of our cases are shown in Table 6, and the preponderance of reversible lesions is apparent. In the indeterminate group are patients in whom follow-up was not adequate enough to be certain of the ultimate outcome, but based on the available information most of these also appeared to be of the reversible category. Although relatively few of our patients had persistent colitis, the proportion of such cases in future series probably will increase with greater recognition of the vascular etiology of most cases of colitis in the aged. Until recently the lack of appreciation of the histologic appearance of ischemic colitis has prevented most pathologists from making this diagnosis except in the presence of stricture or gangrene.

Ischemia may involve any portion of the colon, but the splenic flexure, descending colon and sigmoid colon are the most commonly involved sites (Fig 17). While the distribution and pattern of involvement do not bear any relationship to the severity of the ischemia, specific causes of ischemia do appear to more commonly affect certain areas. Iatrogenic ischemia resulting from ]igation Of the IMA usually produces changes in the sigmoid colon, while low flow states show a predilection for the splenic flexure. Simi- larly, the length of bowel involved varies with the cause, i.e, atheromatous emboli often result in short segment changes ~ and low flow states produce much longer ones.

While British authors initially considered rectal involvement -[- .

rare or nonexistent, 5~ in our experience and that of others it is a relatively frequent finding. Although Farman ~c' found that rectal ischemic disease was always accompanied by involvement of the sigmoid colon, we have seen several instances of isolated rectal changes. In one patient this led to a short rectal stricture with normal bowel proximally. The wide variations in the site and

TABLE 6.-CLINICAL CLASSIFICATION OF 150 PATIENTS WITH COLONIC ISCHEMIA

T R A N S I E N T PERSISTENT ISCHEMIC . G A N G R E N E OR END RESULT (REVERSIBLE) COLITIS STRICTURE PERFORATION U N D E T E R M I N E D

No. of patients 67 28 19 28 8

45

Fig 17.-Distr ibut ion and length of involvement in 150 cases of colonic ischemia. More frequent involvement of left half of colon is apparent.

degree of ischemic changes are understandable in view of the many causes of colonic vascular insufficiency. Known second episodes of ischemia occurred in only 2 of our 150 patients, but these probably occur more commonly than this figure suggests.

ETIOLOGY

Intestinal blood flow can be compromised by alterations in the systemic circulation or by anatomical or functional changes in the local mesenteric vasculature. In the colon ischemia results from many causes: iatrogenic and noniatrogenic, occlusive and nonocclusive, and systemic and local (Table 7). Although a cause of the colonic ischemia or a site of occlusion frequently has been recognized, no specific cause or occlusion has been identified in the majority of cases. The "spontaneous" episodes (generally classified as nonocclusive mesenteric ischemia) have been attributed to low flow states, small vessel disease or both in concert. While low flow certainly can be implicated in those patients with congestive failure, digitalis toxicity or cardiac arrhythmias, these conditions usually have not been present. The greater frequency of colonic ischemic lesions in older age groups suggests a relationship to degenerative changes in the vascular tree, although angiography in these disorders only rarely has demonstrated a significant occlusion or abnormality. Present angiographic techniques, however, do have severe limitations in evaluating the status of smaller vessels. Narrowing of small arteries, arterioles

46

TABLE 7.-CAUSES OF COLONIC ISCHEMIA

1. Inferior mesenteric artery thrombosis 2. Arterial embolus 3. Cholesterol emboli 4. Cardiac failure or arrhythmias 5. Shock 6. Digitalis toxicity 7. Volvulus 8. Periarteritis nodosa 9. Systemic lupus erythematosus

20. Iatrogenic Causes a. Aneurysmectomy b. Aortoiliac reconstruction c. Gynecologic operations d. Exchange transfusions

10. Rheumatoid arthritis 11. Necrotizing arteritis 12. Thromboangiitis obliterans 13. Strangulated hernia 14. Oral contraceptives 15. Polycythemia vera 16. Parasitic infestation 17. Allergy 18. Trauma-blunt and penetrating 19. Ruptured ectopic pregnancy

e. Colon bypass f. Lumbar aortography g. Colectomy with inferior mesenteric

artery ligation

and veins probably is a factor in "nonocclusive mesenteric ischemia," and certainly this term does not imply that the mesenteric vessels are normal. Histologic evidence of such narrowing in the small colonic vessels has been demonstrated and indicates the probable existence of increased resistance and restriction to free blood flow prior to the acute insult. What finally triggers the ischemic episode is still conjectural in most instances. Whether increased demand by the colonic tissues is superimposed on an already borderline flow, or whether flow itself is acutely diminished has yet to be determined.

One possible factor predisposing the colon to ischemia is an inherently lower blood flow than that of the small intestine. Ge- ber, 57 using an electromagnetic flowmeter, found normal colonic blood flow to be 73 ml/minute/100 gin, the lowest of any intestinal segment. Others, 5sG~ using indicator fractionation techniques, have reported conflicting values, both higher and lower, but most investigators agree that the large bowel has a lower flow than the other areas of the gastrointestinal tract. Of even greater importance is experimental evidence that functional motor activity of the colon is accompanied by a decrease in blood flow. This is contrary to the increase in small intestinal blood during periods of digestion and increased peristalsis. Geber has postulated that "the combination of normally low blood flow and decreased blood flow during functiona[ activity would seem to make the colon (1) rather unique among all areas of the body where increased functional activity is usually accompanied by an increased blood flow and (2) more susceptible to pathology." Furthermore, the more pronounced effect of "straining" on systemic arterial and venous pressure in constipated, as compared to normal, patients provides indirect evidence that constipation may accentuate the circulatory effects of defecation. 6~

Colonic blood flow also has been shown to be responsive to changes in environment, eating a meal and emotionally stressful

47

situations2 2 These conditions may either place greater demands on a restricted blood inflow or further decrease an already compromised circulation, In addition, recent experimental studies of the hypothalamic influence on gastrointestinal blood flow in the awake cat suggest that "of the entire gastrointestinal tract, the colon blood flow is most affected by autonomic stimulation. ''~

CLINICAL FEATURES

Most episodes of colonic ischemia produce clinical, radiologic and pathologic changes that are completely reversible. Recog- nition of the nature and reversibility of these lesions will prevent unnecessary operations and the use of improper medical therapy that may aggravate an otherwise self-limiting condition. Irreversible damage resulting in gangrene, perforation, stricture or chronic colitis may have the same clinical onset as reversible episodes, but the greater severity of the lesion soon becomes apparent.

Typically, colonic ischemia presents with sudden onset of mild lower abdominal pain, usually crampy in nature and localized to the left side. The pain is frequently accompanied by tenesmus and is followed within 24 hours by passage of dark or bright red blood from the rectum or by bloody diarrhea. Less commonly, the pain can be severe, especially with irreversible lesions, while in other patients it may be so minimal as to be elicited only by retrospective questioning. Characteristically, the blood loss is minimal. Although massive bleeding has resulted from colonic ischemia, its presence militates against this diagnosis.

Initially, the only physical finding is abdominal tenderness over the area of the involved colon, most commonly the left side. Signs of peritoneal irritation have been noted with ultimately reversible lesions, but if these persist for more than a few hours, they should be considered evidence of irreparable tissue damage. Fever and leukocytosis are usually present and, together with the physical findings, are parameters to be followed in assessing the progress of ischemic lesions. Early and serial barium enema studies are the keys to diagnosing colonic ischemia.

DIAGNOSIS

The initial problem in managing patients with possible colonic ischemia, therefore, is to differentiate them from patients with acute mesenteric ischemia in whom emergency angiography is the first study. In general, patients with acute mesenteric ischemia appear sicker, have more severe pain and usually have a precipitating disorder (Table 8), Patients with colonic ischemia have mild pain, minimal physical findings, minimal bleeding and usually do not have a precipitating problem. The essential char-

48

TABLE 8 . - D I F F E R E N T I A L DIAGNOSIS OF ACUTE MESENTERIC ISCHEMIA AND COLONIC ISCHEMIA

COLONIC ISCHEMIA ACUTE I~IESENTERIC ISCIIEI~IIA

90% in pat ients over 60 years

Acute precipitat ing cause rare

Predisposing associated lesion present in 20%, e.g., colonic carcinoma, stricture, diverticulit is

Do not appear seriously ill

Usually have mild abdominal pain wi th minimal tenderness and guarding

Mild rectal bleeding or bloody d ia r rhea

Should have barium enema first

Most in older age group but may occur in younger pat ients

Acute precipi tat ing cause usual, e.g., myocardial infarct, congestive failure, a r rhythmia , or hypotensive episode

Predisposing lesion uncommon (excluding atherosclerosis)

Usually appear ill

Pain more severe, findings are minimal early in course, but become pronouced la ter

Rectal bleeding and d iar rhea uncommon unt i l late in the course

Should have angiography first

acteristic of patients with colonic ischemia is that they present with only mild to moderate complaints and findings. In some patients the clinical features are not adequate to classify a patient. When this occurs an "air enema" is performed to demonstrate the radiologic signs of colonic ischemia; the use of barium would obscure angiographic visualization of the mesenteric vessels. If the "enema" study is normal, angiography is performed without delay.

If acute mesenteric ischemia is not believed to be present, any elderly patient presenting with sudden onset of abdominal pain and rectal bleeding or bloody diarrhea should have a barium enema within 48 hours of the acute episode. Sigmoidoscopy can be helpful if performed soon after the onset of symptoms, but it is only of value if the segment of involved bowel is within reach of the sigmoidoscope and the typical submucosal hemorrhages are present (Fig 18). The appearance of the mucosa once ulcerations have replaced the hemorrhagic lesions is not specific. We and others have identified colonic ischemia by colonoscopy, but there are theoretical dangers to insufflating gas into bowel that has suffered a vascular insult.

Rectal biopsies are significant only if they show the typical histologic changes of ischemia (present in about half of the specimens that have been obtained). Nonspecific inflammatory changes neither establish nor exclude an antecedent ischemic episode.

A barium enema performed within 48 hours of the onset of symptoms should demonstrate findings to strongly suggest the

49

Fig 18.- Ischemic lesion of rectosigmoid. A, sigmoidoscopic appearance of colon at initial examination. Dark nodular mass is a submucosal hemorrhage below which are ulcerations where other areas of hemorrhage have broken down. B, initial barium enema showing typical "'thumbprints" corresponding to submucosal hemorrhages seen at sigmoidoscopy. C, three weeks later there is complete healing of the rectal mucosa. D, barium enema has returned to normal. (From Littman, et al.: Sigmoidoscopic diagnosis of reversible vascular occlusion of the colon, Dis. Colon Rectum 6:142, 1963. Used by permission.)

diagnosis of colonic ischemia. The pathognomonic "thumbprints," or pseudotumors, that disappear on subsequent studies are the major criteria for a radiologic diagnosis. Two points deserve emphasis: first, the thumbprints represent submucosal hemorrhages (Fig 19, A) and hence are present only in the acute stage of colonic

5O

ischemia (Fig 19, B); and second, since the submucosal hemorrhages are either resorbed or are evacuated when the overlying mucosa breaks down, persistence of radiologically observed defects (thumbprints) excludes the diagnosis of colonic ischemia. A barium enema repeated one week after the initial study should reflect the evolution of the submucosal bleeding, either by return to normal (with resorption), or by replacement of the thumbprints with a segmental colitis pattern. If the initial barium enema is

Fig 19. -A , submucosal hemorrhage, the morphologic basis for " thumbprints" or pseudotumors seen on barium enema after an episode of ischemia. Produced experimentally in a dog by ligation of peripheral vessels. B, superficial ulceration of colon. This lesion is the result of necrosis of the mucosa overlying a submucosal hemorrhage, and demonstrates the transient nature of the hemorrhages and thumbprints.

A

J

51

Fig 20.-Ischemic changes in transverse colon and splenic flexure. A, initial study shows dramatic "thumbprints" throughout area of involvement. B, eleven days later thumbprints are gone and involved colon has typical appearance of segmental colitis including ulcerations (arrow). C, five months after onset there is complete return to normal. Patient was asymptomatic three weeks after her illness (From Boley, S. J., and Schwartz, S. S.: in Boley, S. J., Schwartz, S. S., and Williams, L. F. (eds.): Colonic ischemia; reversible ischemic lesions, Vas- cular Disorders of the Intestine [New York, Appleton-Century-Crofts, 1971.] Used by permission.)

52

delayed until healing has occurred, or the segmental colitis pattern has developed, the ischemic nature of the disease may be missed.

Colonic ischemia cannot be diagnosed on a single evaluation o f a patient, but can only be suspected. A definitive diagnosis is established by following the clinical and radiologic evolution of the patient 's course and his bar ium enema findings. Similarly the prognosis of an episode of colonic ischemia cannot be predicted at its onset unless the physical findings indicate an unequivocal intraabdominal catastrophe.

The nature of ischemic lesions varies, and the final determination in a given case often must be deferred for months (Fig 20). Generally, reversible ischemic lesions fall into two clinical categories, paralleling the evolution of the submucosal hemorrhages (Fig 21). In mild cases the blood is resorbed and complete clinical and roentgenologic healing occurs within one to two weeks. In these patients the symptoms and signs usually subside in 24 to 48 hours. More severe ischemia results in necrosis of the overlying mucosa with varying degrees of ulceration and inflammation. Large and small areas of mucosa may slough with ultimate, complete healing over one to six months. Pat ients with such prolonged lesions may be clinically well even in the presence of persistent changes as seen on bar ium enema studies.

Irreversible lesions may become obvious in hours when gangrene or perforation develops, or follow a protracted course when chronic colitis or stricture develops (Fig 22). Chronic colitis produces persistent diarrhea with occasional blood loss and may go on to delayed perforation; less commonly a protein-losing entero-

Fig 2 1 . - Common clinical courses of reversible ischemic lesions of the colon.

COLONICISCHEMIA

REVERSIBLE DAht~GE

ROENTGENOLOGICAL~ AND CLINICAL

HEALING (1 - 2 weeks)

/','~ILD ABDOMINAL PAIN. " 1 ( " h'~ORE SEVERE PAIN, TENDERNESS. RECTAL ~ i ~ " TENDERNESS. FEVER

BLEEDING AND DIARRHEA J I AND BLEEDING

* J L 1 �9 THU~'LBPRINTS IHUN~BPRINTS

1 SEGMENTAL COLITIS SEGMENTAL COLITIS

! l HEALING 1-6 K~ONll'IS HEALING 1 -6 h'~ONl~S

53

COLONIC ISCff~IA

IRREVERSIBLE DA~,~GE

ABDOh~INAL SIGNS ~ILD ABDOh'~II~L pAIN PERSISTE~T DIARRHE~ OF PERITONITIS TEnDERnESS, RECTAL BLL"EDI~G. FEVER .~D

GAt~GR~E /d~D SEG&'&NTAL ULCERATIVE COLITIS SEG,V,~TAL ULCERATIVE COLITIS PERFORATIO~'~ | (CHRONIC] ( | -4 DAYS) ~r

INCREASING OBSTRUCTION

1 STRICIURE

(1 - 12 t,~ONI~S)

) CANGR~E A,'~0 PERFORAT ION (I o4 V,'EEKS )

Fig 22. - Comrnon clinical courses of irreversible ischemic lesions of the colon.

pathy may result. Strictures usually develop over weeks to months and may produce increasing bowel obstruction.

The diagnosis of colonic infarction is made on the basis of abdominal tenderness, guarding, rebound tenderness, a rising fever, leukocytosis and evidence of paralytic ileus. These signs are not specific for infarction, but dictate the need for emergency laparotomy.

Chronic irreversible ischemic damage may be difficult to diagnose if the patient was not seen during the acute ischemic episode. Barium enema studies may show a segmental ulcerative colitis pattern, a stricture simulating a carcinoma, or even an area ofpseudopolyposis (Fig 23). Patients ' clinical courses at this stage are also often indistinguishable from other forms of colitis or stenosis. If the course has been followed since the acute episode, the ischemic nature of the lesion should be obvious; if not, the de novo occurrence of a segmental area of colitis or stricture in an elderly patient should be considered ischemic and treated accordingly.

Even the pathologist may be unable to distinguish the nature of an area of colitis in resected bowel, as there are no absolute histologic criteria to separate ischemic colitis, Crohn's disease and idiopathic ulcerative colitis. Whether one considers segmental colitis in the elderly an atypical form of idiopathic ulcerative colitis or ischemic colitis, the natural history of this enti ty is tha t of ischemic colitis; the involvement remains localized, resection is not followed by recurrence and the response to steroid therapy is usually poor.

54

Fig 23.-Barium enema appearance of irreversible ischemic lesions of the colon. A, ischemic stricture with characteristics of carcinoma. (Courtesy of L. Kesner, Buenos Aires, Argentina.) B, chronic segmental ischemic colitis. C, pseudopolyposis in segment of ischemic colitis.

TREATMENT

Proper treatment of ischemic lesions of the colon is based on early diagnosis of ischemic damage and continued monitoring of the patient and the radiologic appearance of his colon. The first step in therapy, therefore, is the performance of a barium enema early in the course. I fa presumptive diagnosis of colonic ischemia is made, and the physical findings do not suggest intestinal gangrene or perforation, the patient is observed for changes in his abdominal signs, feveror a rising white blood cell count. System-

55

ic antibiotics are administered and blood and fluids replaced when indicated. In the early stages of the disease it is best to place the bowel at rest and provide .fluids intravenously. If the colon appears distended, it is decompressed with rectal tubes and careful saline irrigations, as increased intraluminal pressure may further compromise the intestinal blood supply. Contrary to their efficacy in ulcerative colitis, corticosteroids are not only of no value but are contraindicated because they increase the possi- bility of intestinal perforation and secondary infection.

Fig 24.-A, ischemic stricture of sigmoid colon. B, eighteen months later, stricture is still obvious. C, two years after initial study colon has almost returned to normal. (Courtesy of L. Kesner, Buenos Aires, Argentina.)

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Serial barium studies of the colon are an essential part of the therapy since they definitely establish the diagnosis of ischemia, and either will verify the reversibility of the colonic damage or demonstrate progression to an ischemic colitis or stricture.

If deterioration in the clinical course is suggested by increasing abdominal signs, fever and leukocytosis, or if the diarrhea, bleeding or both persist for more than two weeks, irreversible damage almost certainly has occurred and surgical intervention is indicated. Reversible lesions should improve within 7 -10 days, and continued symptoms beyond this period warrant a change from a very conservative therapeutic approach to a very aggressive one. In our experience, such patients with persistent diarrhea and bleeding have often gone on to perforation and peritonitis.

An asymptomatic patient with a stricture should be observed, as strictures may improve spontaneously after several months (Fig 24). When symptoms of obstruction are present, however, surgical intervention is necessary.

The operative treatment of irreversible ischemic lesions of the colon is local resection of only the involved area with restitution of intestinal continuity by primary anastomosis. The specimen should be opened immediately by the surgeon or by the pathologist to be certain that all of the involved colon has been removed. Bowel that appears normal externally may have mucosal damage, and all such colon should be excised. Anastomoses through injured colon may leak, and if ischemic bowel is retained it may

go on to stricture. Thus, the treatment ofcolonic ischemia consists of early identi-

fication and continued surveillance, a nonsurgical approach where reversibility is probable, and a decisive surgical approach where permanent ischemic damage is strongly suspected.

COLONIC ISCHEMIA AND POTENTIALLY OBSTRUCTING LESIONS OF THE COLON

Colitis developing acutely in a patient with carcinoma of the colon has been a well-documented occurrence for many years24, ~5 The colitis almost always has been proximal to the tumor and has been reported with and without clinical evidence of intestinal obstruction. With increasing experience this colitis has been recognized to be ischemic in origin; other forms of ischemic colonic damage, e.g., transient intramural hemorrhage and infarction, also have been observed in association with carcinomas and other potentially obstructing lesions of the colon (Table 9). 6G, ~7 The occurrence of ischemic damage below as well as above the associated lesion has also been observed and when the ischemic area is proximal, normal colon usually has been present between the tumor and the involved bowel (Fig 25).

In our series approximately 10% of patients with colonic isch- 57

TABLE 9.-POTENTIALLY OBSTRUCTING LESIONS CAUSING COLONIC ISCHEMIA

1. Carcinoma 2. Diverticulitis 3. Volvulus 4. Hirschsprung's disease 5. Fecal impaction 6. Fecalith 7. Chagas' disease 8. Operative stricture 9. Postoperative fistuleetomy

10. Ischemic stenosis 11. Radiation stricture

emia had an associated carcinoma and another 10% had some other condition tha t interfered with normal colonic motility. This incidence of ischemia in patients with other colonic lesions far exceeds that in the general population and suggests tha t these lesions play some role in the etiology of the colonic ischemic episode.

The mechanisms by which potentially obstructing lesions could effect diminished colonic blood flow are threefold and would be superimposed on the predisposing factors for colonic ischemia previously discussed. Any degree of overt obstruction with distention would bring into play the profound effects of sustained increased intraluminal pressure on blood flow, not only to the involved bowel but to the rest of the intestines. Even in the absence

Fig 25.--A, barium enema showing area of ischemic colitis in descending colon and a nonobstructing carcinoma in the sigmoid colon. B, gross specimen from same patient demonstrating typical segmental ischemic ulcerative colitis. Normal bowel between the neoplasm.

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of distention, t ransient bu t repeated elevations in intraluminal pressure may occur proximal to partial obstructions during peristalsis, with similar deleterious changes in blood flow. The presence of a carcinoma or other lesion in the lower Colon, even without obstruction, may affect colonic motility and alter the defeca- tory pattern, with increasing hypermoti l i ty and ul t imately constipation and straining. Thus, colonic blood flow may be decreased by (1) increased intraluminal pressure; (2) hyperperistalsis and increased muscular spasm in the colon with their direct effect on the mural and mucosal circulation; and (3) straining, with its associated increase in intraabdominal but extraenteric pressure, and diminution in aortic blood pressure and vena caval flow. The addition of one or more of these factors to a colon with an already precarious blood supply might indeed precipitate an ischemic episode.

Clinically, patients with colonic ischemia superimposed on a carcinoma or other lesions may present with symptoms only of the pr imary disorder, e.g., with a neoplasm, crampy pain of a chronic nature or acute colonic obstruction. In most cases, however, the predominant complaints are related to the ischemic epi- s o d e - s u d d e n onset of mild to moderate abdominal pain, fever, bloody diarrhea and abdominal tenderness.

It is imperative for both radiologists and surgeons to be aware of the frequent association of colonic ischemia and other lesions of the large bowel. The radiologist must be careful to exclude other lesions in every case of colonic ischemia, for in two of our pat ients nonobstructing neoplasms were overlooked on the initial bar ium enema. For the surgeon it is vital to examine any colon removed for carcinoma to exclude the presence of an ischemic process in the area of the anastomotic line, because such involvement may lead to leaks or strictures.

PROGNOSIS

The outlook for patients with colonic ischemia is generally good. Recurrent episodes probably occur in less than 5% and we have not seen late sequelae in patients whose initial clinical complaints and roentgenographic abnormalities have subsided. Areas of ischemic colitis and even apparent strictures have re- solved without t rea tment after many months. The high risks of developing a stricture as projected by one author, 68 are completely contrary to our experience with 150 patients, only a small fraction of whom required an operation.

FOCAL SEGMENTAL ISCHEMIA OF THE SMALL BOWEL

In contradistinction to the catastrophic vascular insults discussed in the previous section on acute mesenteric ischemia,

59

those localized to short segments of the small bowel produce a broader spectrum of clinical features bu t without the life-threat- ening systemic complications (shock, hypovolemia, fluid and elec- trolyte imbalance, and myocardial depression) associated with ischemia of more extensive portions of the gut. Although the ma- jori ty of patients with focal ischemia present with chronic complaints arising from the sequelae of the acute episode, some present with sudden abdominal pain and physical signs of an acute abdomen; the clinical presentation depends on the degree ofischemic damage.

ETIOLOGY AND PATHOPHYSIOLOGY

The causes of ischemia to short segments of the small intestine are diverse (Table 10), but the final effect on the bowel is the same. The most frequent causes are atheromatous emboli, strangulated hernias, collagen diseases, blunt abdominal t rauma, segmental venous thrombosis and, especially during the 1960s, enteric-coated thiazide-potassium chloride preparations. "~-7l Those lesions associated with systemic diseases may occur late in the course of the illness or may be the heralding event of the generalized disorder.

With focal ischemia there is usually adequate collateral circulation to prevent t ransmural hemorrhagic infarction. Hence, the commonest lesions are infected infarcts resulting from partial necrosis of the bowel wall and secondary invasion by the intestinal bacterial flora. Although the normal mucosa is resistant to bacterial invasion, a minimal vascular insult may destroy this natural barrier. Limited tissue necrosis may result in complete healing, a chronic enterit is simulating Crohn's disease or a stricture with partial or complete intestinal obstruction. Strictures are indicative of damage and fibrosis that include the muscularis propria. When the local insult is severe enough to produce transmural necrosis, perforation or a localized peritonitis may ensue. The final outcome of an episode of focal ischemia depends on both the degree of ischemic necrosis and the virulence of the secondary infection.

In 1960, reports from many parts of the world described a typical short circumferential stricture producing obstruction (Fig 26, B). The clinical observation of the association of these lesions with the ingestion of enteric-coated thiazide tablets containing potassium chloride was first made by Lindholmer et al. G9 in Swe- den and Baker et al. 7~ in the United States. Animal experiments established the potassium chloride as the responsible agent, and demonstrated that the lesions were localized venous infarcts that progressed to stricture. 72, 73 Later clinical studies revealed that in some patients these tablets had caused more severe infarcts with acute perforation.

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TABLE 10.--CAUSES OF FOCAL ISCHEMIA OF THE SMALL BOWEL

Immune Complex disorders (collagen-vascular disease) Systemic lupus erythematosis Polyarteritis nodosa Rheumatoid arthritis Dermatomyositis Sj~gren's syndrome Progressive systemic sclerosis

Angiitis Infective

Tuberculosis, syphilis, ascariasis, leprosy, typhoid, HbsAg Hypersensitivity (Churg-Strauss) Postcoarctation syndrome

Vasospastic Malignant hypertension Pheochromocytema

Degenerative ArterioscLerosis Diabetes mellitus

Miscellaneous diseases Hereditary hemorrhagic telangectasia (Rendu-Osler-Weber) Pseudoxanthoma elasticum (GrSnblad-Strandberg) Cutis hyperelastica (Ehlers-Danlos) Malignant atrophic papulosis (KShlmeier-Degos) Angiokeratoma corporis diffusum (Fabry) Thrombotic thrombocytopenic purpura (Moschcowitz) Thromboangitis obliterans (Buerger) Anaphylactoid purpura (Henoch-SchSnlein) Amyloidosis Polycythemia vera Wegener's granuloma Radiation Trauma Mechanical (incarcerated hernia) Carcinoma Focal mesenteric venous thrombosis

Drugs Oral contraceptives Bishydroxycoumarin anticoagulants Ergot alkaloids Enteric-coated potassium

CLINICAL FEATURES

Patients with short segment ischemia may present in one of three clinical patterns that reflect the severity of the infarct. In the acute presentation, seen with t ransmural necrosis, there is a sudden onset of abdominal pain tha t often simulates an attack of acute appendicitis. Initially, the pain is crampy but then becomes constant and aching. Although it most often is described as periumbilical, the localization varies with the segment of small bowel involved. Physical findings are those of an acute abdomen, and on occasion an inflammatory mass can be palpated. Positive laboratory findings are limited to a leukocytosis that may be minimal or severe. Gross bleeding from the rectum in uncommon, al-

61

+ - mmm+m,mmmmmll I 't �9 I . ~ . . . . . . . . v+_~._'?X'~. ' ' + + ~+-~_++_-,_ + _ _ - - ~ . ~ . . . . . . . . . . :_ . . . . . . .

Fig 26.-A, moderate obstruction with characteristic roentgen appearance of healed infarction. Dilatation distal to the lesion would suggest the presence of a second site of narrowing, not demonstrated. B, gross specimen from patient showing short circumferential stenosing ulcer typical of those occurring secondary to ingestion of enteric-coated potassium. (From Schwartz, S. S., and Boley, S. J.: in Boley, S. J., Schwartz, S. S., and Williams, L. F. (eds.): Radiologic features of vascular disorders of the small intestines as demonstrated by barium study, Vascular Disorders of the Intestine [New York, Appleton-Century-Crofts, 1971.] Used by permission.)

though tests for occult blood are often positive. Roentgenographic findings vary widely. Plain films of the abdomen early in the course are usually normal, but later may reveal a "sentinel loop" or a nonspecific ileus pattern. Free air is rarely present. Small bowel opacification studies usually are not performed be-

62

cause of the physical findings, but when done may reveal the characteristic signs of acute intestinal ischemia, i.e., thumbprint- ing, spasm or ulceration. TM

Another group of patients present with signs and symptoms of chronic enter i t is-crampy abdominal pain, diarrhea, occasional fever and weight loss. The clinical picture may be indistinguishable from that of Crohn's disease of the small bowel. Even the roentgenographic findings of a segmental area of thickened bowel with mucosal nodularity, ulceration and narrowing are similar. The only diagnostic feature that may be of some help is the location of the involved segment; Crohn's enteritis usually but not always includes the terminal ileum, whereas focal ischemia occurs anywhere in the small bowel. Even at operation the lesion may have the gross appearance of Crohn's disease.

The most common presentation is that of chronic small bowel obstruction with or without a history of some antecedent episode of trauma, pain or hernia incarceration. Intermittent abdominal pain, distention and vomiting are direct results of the obstruction, and bacterial overgrowth in the dilated loop proximal to the obstruction may lead to the metabolic and clinical derangements usually associated with the "blind loop syndrome," i.e., anemia, diarrhea and steatorrhea. 75 Radiologic studies reveal a smooth tapered stricture of varying length with an abrupt change to normal bowel distally and dilated bowel proximally (Fig 26, A). Mucosal ulceration may be present in the strictured area but without the overhanging edges and mucosal destruction characteristic of malignancies. Laboratory studies may reflect the metabolic abnormalities previously mentioned including anemia and malabsorption, and may also reveal marked hypoproteinemia. Even short segments of ischemic intestine may result in an albumin-losing enteropathy that cannot be managed by conservative means.

DIAGNOSIS AND TREATMENT

A preoperative diagnosis of focal ischemia is difficult to make 'without a careful history. A previous episode of transient pain, trauma, incarcerated hernia or a known systemic illness can suggest the correct diagnosis. A detailed history of medication is essential, for although the original potassium preparations that produced small intestinal lesions have for the most part been removed from the market, those still available can cause ulceration, albeit less frequently. None of the physical, roentgenographic or laboratory findings are specific, so in most cases the diagnosis is made by the surgeon or the pathologist.

The treatment for acute focal ischemia is usually surgical but some patients without signs of peritonitis can be managed expectantly. In those instances the diagnosis is based on the roentgeno-

63

graphic findings of thumbprints indicative of acute ischemia, and serial studies should reveal a changing pattern. Patients treated conservatively are maintained on fluids administered intravenously, nasogastric suction and parenteral antibiotics. Both clinical and roentgenographic findings must resolve or the nonsurgical approach is abandoned.

Patients who present with chronic enteritis or obstruction should be operated on immediately after proper preparation. Surgeons should be aware of the lesions of segmental ischemia because a limited resection is the operation of choice both for ob'- structing lesions and for focal enteritis. Many "baffling cases of Crohn's disease" described in the past were actually infected infarcts and the incorrect diagnosis frequently led to an inappro- priate operation. Most focal ischemic lesions are ultimately identified by the pathologist, but even he may misinterpret the true nature of the histologic findings because of the prominent inflammatory reaction associated with intestinal infarcts. The intensity of this inflammatory reaction is unique to infarction of the bowel because of the mass of bacteria within its lumen. As with ischemic lesions of the colon, the nonspecific microscopic characteristics of chronic ischemic changes in the small bowel are only now being widely recognized.

CHRONIC INTESTINAL ISCHEMIA (abdominal angina, intestinal angina, recurrent mesenteric ischemia)

Inadequate intestinal blood flow may result in functional derangements or impair the structural integrity of the bowel. In- cluded under the heading of chronic intestinal ischemia are those conditions in which there is insufficient blood flow to satisfy the demands of the increased motility, secretion and absorption that develop after meals. These disorders manifest themselves either by ischemic visceral pain Qr abnormalities in gastrointestinal absorption or motility. Patients with chronic intestinal ischemia are actually experiencing recurrent acute episodes of insufficient blood flow during periods of maximal intestinal work load. Therefore, the pain is similar to that arising in the myo- cardium with angina pectoris, or in the calf muscles with intermittent claudication.

The symptoms of chronic or recurrent mesenteric ischemia have been recognized since Schnitzler's original description in 1901, TM but it was not until 1921 that Klein suggested our present understanding of the basis of the pain and proposed the term mesenteric intermittent claudication. 77 Since that time numerous reports have called attention to the syndrome of "abdominal angina" or intermittent abdominal pain from intestinal ischemia. More recently the association of malabsorption and ischemia has been documented in a few casesF s

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Chronic intestinal ischemia has been reported with aneurysms of the aorta, celiac axis (CA) and SMA, with congenital and trau- matic arteriovenous fistulas involving the SMA and hepatic arteries, with coarctation of the aorta and with congenital anoma- lies of the splanchnic vessels. Such cases are rare, however, and atherosclerotic involvement of the mesenteric vessels is almost always the cause of this form of intestinal ischemia.

ATHEROSCLEROSIS OF THE CELIAC AND MESENTERIC ARTERIES

Atherosclerosis commonly involves the splanchnic arteries in individuals over 45 years of age. In a review of their own and previous autopsy studies, Reiner and Jiminez TM found the SMA, IMA, CA and splenic arteries to be the most frequently involved of the splanchnic vessels. In one of their studies atherosclerosis of the splanchnic vessels was noted in 68 of 88 autopsies, and in 44 of them some degree of stenosis was observed in one or more of the SMA, CA and IMA. Narrowing of the major vessels was almost always due to a plaque at the aortic ostium or in the proximal 1 - 2 cm of the artery. Severe stenoses were uniformly associated with marked aortic atherosclerosis. Total occlusions were noted in 15 instances, but occurred mostly in cases in which there were no intestinal infarctions. There was little correlation between the degree of mesenteric atherosclerosis and the clinical course, but as expected, patients with severe mesenteric involvement had a higher incidence of coronary ar tery disease and diabetes mellitus.

Although autopsy and angiographic studies have established the frequency of partial or complete occlusion of the SMA, CA and IMA, there have been relatively few patients with documented chronic intestinal ischemia. Moreover, there are many patients with occlusion of two or even all three of these vessels who remain asymptomatic (Fig 27). Hence, the clinical significance of the angiographic demonstration of occlusion of one or more of these vessels remains controversial. The lack of any objective means to determine the inadequacy of intestinal blood flow before morphologic changes of ischemia occur is the major obstacle to identifying patients with chronic mesenteric ischemia.

Dick et al2 ~ at tempted to establish objective guidelines for the presence of chronic mesenteric ischemia by angiographic measurements of the total cross-sectional area of the SMA, CA and IMA in control patients, in hypertensive and arteriopathic patients and in patients with chronic intestinal ischemia.

These authors found that all patients with intestinal ischemia had total cross-sectional areas reduced to below two-thirds of normal. However, patients without ischemia had similar reduc- tions. The inexact nature of such measurements is obvious. More- over, the length of the stenosis, which is also an important factor, was not considered. A major shortcoming of evaluating intestinal

65

Fig 27.-Angiogram from patient with no abdominal symptoms. A, flush aortogram in lateral position shows occlusion of celiac axis, superior mesenteric artery (SMA) and inferior mesentedc artery. B, A-P flush aortogram demonstrates filling from middte hemorrhoidal arteries up to a large "'meandering artery" with ultimate filling of SMA and celiac axis through these collateral channels.

blood flow from the patency of the individual major vessels is the equal importance and variability of the collateral blood supply. The significance of stenoses of the major arteries is reduced in the presence of prominent collateral anastomoses, but is of great importance in their absence.

The most important sources of arterial communication between the CA and SMA are the pancreaticoduodenal arcades. These are formed by the superior pancreaticeduodenal arteries from the celiac circulation and the inferior pancreaticoduodenal arteries from the SMA. Enlargement of this collateral loop may be visualized on upper gastrointestinal opacification studies when it produces extrinsic pressure on the medial aspect of the descending duodenum. The main collateral between the SMA and IMA is the communication between the middle colic artery and the ascend- ing branch of the left colic artery. When this channel assumes importance it becomes dilated and tortuous and is known as the "meandering artery" because of its appearance in the mesentery of the left colon. Although sometimes referred to as part of the "marginal vessel of Drummond," it more accurately is a dilated "arc of Riolan." Determination of the presence or absence of these collateral circuits is an integral part of the angiographic evaluation of possible chronic intestinal ischemia. The absence of collar-

66

erals with occlusion of the SMA or CA is an ominous sign and suggests an acute rather than a chronic process.

CLINICAL FEATURES.--The one consistent clinical feature of chronic mesenteric ischemia is abdominal discomfort or pain. Most commonly this occurs 10-15 minutes after eating, gradually increases in severity, reaches a plateau and then slowly abates in 1- 3 hours. The pain is most often cramping in nature, is located in the upper abdomen and may radiate from the epigastrium through to the back. A more constant and diffuse aching has also been described. Some patients can relieve their pain by squatting or assuming a prone position. Initially the pain occurs only after a large meal, but characteristically there is a progressive increase in both the frequency and severity of attacks with time. The pain pattern is so intimately related to the ingestion of food that the patient will reduce the size of his meals Csmall meal syndrome"), become reluctant to eat and even develop frank sito~ phobia. The result of this is significant and often massive weight loss.

Bloating, flatulence and derangements in motility with constipation or diarrhea are also seen. Intermittent episodes of vomiting occur less commonly. Steatorrhea with the typical ~'stool floating in water" is observed by approximately one half of the patients.

Physical findings are both limited and nonspecific. The patient appears chronically ill with signs of marked weight loss. The abdomen is soft and nontender even during episodes of pain, but significant distention may be observed. A systolic bruit is heard in the upper abdomen in approximately one half of the patients. Many patients will have a history or physical manifestations of associated cardiac, cerebral or peripheral vascular insufficiency.

DIAGNOSIS.--There is no specific reliable diagnostic test for abdominal angina at this time. The diagnosis must be based on the clinical symptoms, the arteriographic demonstration of an occlusive process of the splanchnic arteries and, to a great measure, on the exclusion of other gastrointestinal disease.

In view of the imprecise criteria for identifying chronic intestinal ischemia, the nature and postcibal character of the pain and the degree of weight loss are of paramount diagnostic importance. Patients with atypical symptoms should be observed as the typical pain pattern will usually develop with time if arterial insufficiency is present.

Conventional radiographic examinations of the gastrointestinal tract are usually unremarkable, but may reveal evidence of decreased motility in the form of puddling of barium in the jejunum. Demonstration of extrinsic pressure defects along the medial border of the descending duodenum indicates the presence of large collaterals between the SMA and CA. Studies for malab-

67

sorption will usually show increased fecal fat, decreased urinary excretion of D-xylose and, less often, increased fecal nitrogen. Although these tests identify absorption defects, none are specific for malabsorption due to ischemia. Abnormalit ies also have been detected in small bowel biopsies, but again no finding is specific for ischemic diseases. Occult blood in the stools is frequently present at some stage of the disease.

Angiographic evaluation includes flush aortography in frontal and lateral views and selective injections of the SMA, CA and, if possible, the IMA. The degree of occlusive involvement of the three major arteries can be best assessed on the lateral projec- tions, and the collateral circulation and pat tern of flow are best seen on the frontal views. The presence of prominent collateral vessels indicates a significant stenosis of a major vessel, but also connotes a chronic process. As has been emphasized, angiographic demonstration of stenoses or occlusions of one or two or all of the major vessels does not by itself establish the diagnosis of arterial insufficiency.

A recent method of assessing the adequacy of-splanchnic blood flow, which appears promising, has been described by Hansen et al. s~ Splanchnic blood flow is defined as the total blood flow through the three splanchnic arteries and extra-splanchnic collaterals. It is determined by measuring hepatic blood flow with indocyanine-green, both in the fasting state and after a standard meal. Oxygen consumption in the splanchnie bed is also measured. In their study of 15 patients with abdominal pain, there was a significant failure of patients with abdominal angina to increase their splanchnic blood flow after the test meal. After arterial reconstruction the postprandial increase was similar to that in the control group. This technique is a "rather demanding procedure in terms of laboratory facilities and expertise" and involves catheterization of the radial artery, an arm vein and an hepatic vein. In spite of this, if the observations of Hansen et al. are corroborated, this method will provide an objective means for determining the need for operation.

INDICATIONS FOR OPERATION. -- With no available method for measuring intestinal blood flow, precise criteria to define the need for operative arterial reconstruction are lacking. There is agreement that a patient with the typical pain of abdominal angina and unexplained weight loss, whose diagnostic evaluation has excluded other gastrointestinal disease and whose angiogram shows occlusive involvement of at least two of the three major arteries, should have the benefit of the operation. The is- sue is much less clear if only one major vessel is involved or if the nature of the clinical presentation is atypical. Until a quantitative test such as that described by Hansen and his associates becomes available, we would observe a patient with atypical syrup-

68

toms. However, we would operate on a patient with the typical clinical picture, but with only one major vessel occluded on anglo- gram, if the severe pain and weight loss did not respond to any other treatment.

In the past a major indication given for early operative intervention was the prevention o f acute intestinal infarction. This concept was based on the impression first expressed by Dunphy in 1936 s2 and reaffirmed by Mavor et al. in 1962, ~ that up to 50% of patients with acute mesenteric infarction had preceding abdominal symptoms. The implications of these observations, which have been expressed repeatedly in the li terature, are tha t patients with abdominal angina go on to infarction, and that operat- ing on symptomatic patients will decrease the occurrence of infarction. Neither of these concepts is fully supported by more recent experiences. As previously discussed, over 75% of cases of acute mesenteric ischemia are due to embolus or nonocclusive disease, and in neither condition are prodromal symptoms present. Therefore, only a fraction of that minority of patients who have an SMA thrombosis have had a history of earlier pain.

The answer to the converse question, i.e., how many patients with symptoms of chronic mesenteric ischemia go on to an acute infarction, is not known. Neither has the incidence of intestinal infarction in patients with occlusive disease of the splanchnic vessels ever been established. Reiner and Jimenez concluded from their autopsy studies that occlusive disease is probably an uncommon cause of intestinal infarction, with emboli being far more common/~ Hence, the fear of impending intestinal infarction is not an indication for operation, if other criteria do not warrant it,

Although to the best of our knowledge no cases have been reported with significant malabsorption in the absence of abdominal pain, it is theoretically possible that such a syndrome might exist in a patient with two-vessel stenosis. In such a case the risk of major arterial reconstruction would have to be weighed against the metabolic significance of the malabsorption process, if uncor- rectable by medical measures.

There is one special situation in which reconstruction or bypass of obstructed splanchnic arteries is indicated in the absence of abdominal complaints. This indication arises in a patient who is undergoing an aortic operation for peripheral vascular disease and in whom aortography has demonstrated occlusive involvement of the SMA and/or CA and the presence of a large ~emean- dering artery." In such patients the lat ter artery is supplying most of the blood flow to the splanchnic circulation from the IMA. Since the IMA may be compromised during the aortic procedure, it is advisable to provide another source of blood flow as par t of this operation. The occurrence of acute intestinal ischemia result-

69

ing from "aorto-iliac steal syndromes" has also been described in this situation after successful restoration of blood flow to the legs, but when no procedure has been performed on the visceral yes- sels. Although we question whether or not the acute intestinal ischemia in these reports represents a true "steal," the occurrence of this complication indicates the need for prophylactic revascularization of the mesenteric vascular bed in this situation.

Even when one of the aforementioned indications for arterial reconstruction is present, careful judgment must be exercised before deciding to operate. The severity of symptoms must be weighed against the added operative risks resulting from the generalized arteriosclerosis and coronary artery disease in that individual patient. The frequent coexistence of degenerative changes in the aorta and the iliac arteries, e.g., aneurysmal and occlusive disease, increases the difficulties and dangers ofmesenteric revascularization and must be taken into account in determining the operative risk and in planning the operative approach.

SURGICAL MANAGEMENT.- Since 1958, several procedures have been advocated for restoring normal flows and pressures distal to an occlusion in the CA or SMA. Endarterectomy of the proximal CA and SMA was the first method advocated for electively treating chronic mesenteric ischemia. 8~ Although widely used initially, the procedure has been found to be technically difficult. Good exposure of the origins of the splanchnic vessels is difficult to ob- tain and the occluding atherosclerotic plaque frequently extends into the aorta and cannot be effectively removed through an arteriotomy in the CA or SMA. The results of the endarterectomy procedures, whether or not a vein or Dacron patch was used to close the arteriotomy, were poor and the procedure has generally fallen into disfavor. Of greater importance has been the observation that with occlusive disease originating from the CA and the SMA, it is usually unnecessary to restore flow to more than one of these two arteries.

The present preferred procedure for arteriosclerotic occlusive or stenotic disease of the CA and SMA is a bypass to the latter vessel. The procedure is designed to provide rapid exposure and to facilitate the performance of the anastomoses (see Fig 15). The SMA is exposed by elevating the transverse mesocolon and re- tracting the small bowel to the right. The retroperitoneum is opened longitudinally over the aorta and upward between the inferior mesenteric vein and the fourth portion of the duodenum. The ligament of Treitz is incised and the aorta and SMA exposed (see Fig 15). The SMA is freed by dissection for 2 -3 cm distal to the origin of the middle colic artery. Care is taken to protect and isolate the middle colic, jejunal and other branches. Heparin is administered (1 mg/kg) and the SMA and its branches are controlled as gently as possible using atraumatic vascular clamps or

70

silicon rubber tapes doubly looped around the vessels~ A linear arteriotomy is made in the SMA in an area that is palpably and angiographically distal to the atherosclerosis. A previously prepared vein or prosthetic graft is cut diagonally, spatulated and sutured to the SMA using closely spaced fine polypropylene sutures. Autologous saphenous vein (reversed) is probably the graft material of choice if, after gentle distention, it is at least 5 mm in its smallest diameter. Knitted Dacron (6-8 mm) is an acceptable substitute, especially if it is to be inserted into a Dacron aortic prosthesis. Polytetrafluoroethylene (Gore-Tex), which appears to show promise in low-flow lower extremity reconstructions, may become the graft material of choice because of its ready availability and low tendency to form a thickened pseudointima.

Upon completion of the graft-SMA anastomosis, the graft is occluded flush with the anastomosis, and the clamps or loops on the SMA are released. An uninvolved area of the aorta, previously selected and circumferentially dissected, is isolated by cross- clamping with vascular clamps and an arteriotomy is fashioned. Partially occluding clamps are often not adequate to control the thick-walled diseased aorta that may be present in these patients. Anastomosis of the graft to the aorta is performed with similar careful technique and all clamps removed. Patency of the graft and the anastomoses is assured by the presence of good pulsations in the distal arteries of the bowel.

Some surgeons believe that in the presence of CA and SMA oc: clusion, adequate surgical management must include restoration of normal pressure to both vessels and their branches, s:' After completion of the SMA revascularization, the pressure in the celiac system distal to the occlusion should be measured. If a significant aortic-celiac pressure gradient persists, they advocate direct revascularization of the CA.

Revascularization of the CA, whether done for an isolated stenosis or as part of a correction of combined splanchnic vessel involvement, can be accomplished in several ways. These include reimplantation of the CA into the adjacent aorta after excision of the occluded or stenotic segment, endarterectomy of the CA with or without vein patch, and end-to-end or end-to-side bypass from the adjacent aorta to the CA distal to the occluded segment (Fig 28). Although these direct procedures can be done through a transabdominal approach, they may be extremely difficult or impossible particularly in obese individuals. Hence, it is often necessary to use a thoracoabdominal incision with reflection of the left upper quadrant structures downward and to the right to provide adequate access to the CA, and to allow dependable control of the adjacent aorta. For this reason, except in the thin patient whose disease does not require aortic control, we prefer the simpler operation of aorta-to-splenic artery vein bypass when revascularization of the celiac axis is required. This procedure can

71

A B C D

Fig 28.-Diagrammatic r~ )resentation of various methods of revasculariza- lion of the celiac axis. A, reimplantation. B, endarterectomy with patch graft. C, graft from distal thoracic aorta to end of undiseased celiac axis. D, resection of stenosis and reanastomosis.

Fig 29.--Technique of aorta-splenic arterial bypass for revascu]arization of celiac axis. A, Toshaped incision in retroperitoneum extending cephalad to right of inferior mesenteric vein and transversely across the root of the transverse mesocolon parallel to the inferior border of the pancreas. B, inferior mesenteric vein has been divided and the lower border of the pancreas retracted upward exposing the posterior surface of the gland. The splenic artery is exposed as it courses along the superior border of the pancreas. Positioning of the vein bypass is shown.

72

uniformly be accomplished transabdominally working entirely below the transverse mesocolon and approaching the splenic artery by reflecting the lower border of the pancreas upward (Fig 29). The remaining details of the procedure are similar to those described for standard retrograde aorto-SMA bypass.

Selection of the site of the aortic anastomosis for a SMA or CA bypass may be rendered difficult by the presence of atherosclerosis. The aorta above the origin of the IMA is generally less involved, but good exposure is more readily obtained distally. A site just proximal or just distal to the origin of the IMA is usually 6p- timal. Care is taken not to injure the IMA, which may be an important collateral. Occasionally the graft will have to be inserted into an iliac artery because of sclerotic or aneurysmal disease of the aorta. More commonly, replacement or bypass of the aorta with a Dacron prosthesis will be required for a concomitant aneurysm or occlusion. In such instances, the aortic procedure is completed and then the SMA graft is inserted into the Dacron prosthesis.

Patency rates with such bypass grafts to the SMA or CA have generally been good and symptomatic relief has been excellentY 6 However, Stoney and his associates 87 have recently reported poor results with retrograde bypasses. They attribute this to an unusual and rapidly progressive form of atherosclerosis that involves the subdiaphragmatic aorta and that occurs more commonly in females and in relatively young subjects. On the basis of thei r series of 34 cases, they advocated a thoracoabdominal retro- peritoneal approach and a '~trap-door" transaortic endarterectomy supplemented with either venous patch grafts when indicated or with antegrade prosthetic grafts originating from t h e u n i n - volved distal thoracic aorta. How often this more complicated approach will prove to be necessary remains to be shown. For the present, this procedure should only be performed in centers having experience with this unusual approach and it should be re- served for the young patient who is free of other manifestations of generalized arteriosclerosis.

RESULTS. - - A l t h o u g h hundreds of cases of elective revascularization of the mesenteric arteries have been reported, long term follow-up information is limited. In three recently reported series comprising 70 patients the operative mortality was 7%; 70% of the patients were relieved of their symptoms2 s'9~ The late deaths occurring in 21% of patients are a reflection of their generalized arteriosclerotic disease. However, only one patient died of intestinal infarction after the immediate postoperative period. In McCollum et al.'s series of 33 patients, 83% were alive five years after operation, and 62% were alive after 10 years2 ~

Properly selected patients with intestinal angina can be operated on successfully with reasonable operative risk and a good

73

long-term prognosis. Most will be relieved of their pain and malabsorption, although complete relief of the latter may take months.78, 9, Although it has not been shown definitely that revascularization will protect against a fatal acute mesenteric infarction, the infrequency of these catastrophies after a successful operation suggests that this may be true.

CELIAC AXIS COMPRESSION SYNDROME (CACS)

This syndrome is included for completeness although we and others do not consider it to be a manifestation of gastrointestinal ischemia. It has been a subject of controversy since Harjola's original description in 1963 of a patient with abdominal pain associated with external compression of the celiac axis22 Two basic questions concerning the syndrome remain unresolved: (1) does the entity really exist as a cause of abdominal pain, and (2) if so, is the pain a result of gastrointestinal ischemia? At the present time there is no conclusive clinical or experimental data that either establish or exclude compression of the CA as a cause of abdominal pain, and there is even less evidence that gastrointestinal ischemia is the cause of the pain described in association with this anatomic abnormality.

ANATOMY.--The CA arises from the anterior aspect of the abdominal aorta at a level that is normally between the lower third of the 12th thoracic vertebra and the middle third of the first lumbar vertebra. Two important anatomic structures that are intimately related to the CA are the median arcuate ligament of the diaphragm and the celiac ganglion (Fig 30, A and C).

The median arcuate ligament is a highly variable structure both in composition and in location. The level at which it crosses the aorta varies with the age, sex and habitus of the patient, but it is usually sufficiently close to the CA so that celiac compression occurs during expiration and is relieved during inspiration (Fig 30, B). Thus, most epigastric bruits in patients with CACS are accentuated during expiration and diminished during inspiration.

The celiac ganglion consists of left and right divisions, the fibers of which interconnect around the CA. In approximately 50% of patients, it joins with fibrous and fatty tissue to form a thick and potentially compressing shield anterior and inferior to the median arcuate ligament (Fig 30, D).

CLINICAL FEATURES.- One of the major difficulties in assessing the validity of the CACS is the different criteria used by various authors to define it. Postprandial abdominal pain, weight loss, diarrhea, an abdominal bruit and angiographic demonstration of extrinsic compression of the CA constitute the findings on which the diagnosis should be based. However, in a recent review of 26

74

B i ~�84

/

/

Fig 30.-Anatomy of celiac axis (CA) compression syndrome. A, normal anatomic position of median arcuate ligament cephalad to the origin of the CA. B, with abnormally high origin of the CA or low position of ligament, the proximal portion of the artery is compressed. C, normal anatomic position of the celiac ganglion. D, compression of proximal portion of CA by ganglion.

75

clinical series comprising 341 patients (Brandt, L. J., and Boley, S. J., in preparation), abdominal pain was the sole consistent symptom, and even an adequate description of the character of the pain was usually found to be lacking. The relation of the pain to eating was mentioned in only 30% of the reports, but in these it was characteristically postprandial.

Descriptions of the pain typical of intestinal angina, i.e., pain beginning 10-15 minutes after a heavy meal and lasting approximately 1-3 hours, were notably absent. The location of the pain, when described, was most often epigastric, but occasionally was in the right or left upper quadrants. Diarrhea and loss of weight were noted in only one-half of the cases and the average weight loss when described was 20 pounds. Upper gastrointestinal symptoms including nausea and vomiting were reported in approximately one-fourth of the patients.

An abdominal bruit, the most important physical sign associated with the syndrome was frequently not mentioned and in rare instances was specifically stated to be absent. Even when an abdominal bruit is present, however, its diagnostic significance must be questioned since epigastric bruits occur in 6.5-15.9% of healthy adultsY 3 It has been suggested that although the presence of the bruit is nonspecific its phonoarteriographic characteristics may be more diagnostic. ~ Conventional radiologic opacification studies of the stomach and small bowel, when reported, were usually normal.

Absorption tests were included infrequently in the diagnostic studies and evidence of malabsorption was only rarely reported. There have been several reports of an association of CA stenosis and pancreatitis, but documentation of improvement after decompression of the artery is lacking. However, in one recent study 9~ 3 of 12 patients with CACS, but no evidence ofpancreati- tis, had abnormal pancreatic function tests that improved after operative decompression.

ANGIOGR~HY.- Some radiologists believe that compression of the CA is best demonstrated by lateral aortography, while others prefer a selective injection into the CA. If a selective injection is employed, care must be taken not to advance the catheter past the point of arterial narrowing. However, even if the stenosis is not seen, its presence can be inferred from collateral flow patterns and subsequently confirmed by lateral aortography. Compression by the crural fibers of the diaphragm, the celiac ganglion or both produces a smooth asymmetric narrowing of the superior aspect of the CA and its possible inferior displacement toward the SMA (Fig 31). These findings vary with respiration due to the caudad movement of the aorta and CA and the ventral movement of the median arcuate ligament during inspiration.

Doubt as to the significance of angiographic demonstration of 76

'!

I=i9 31.-Lateral flush aortogram showing typical compression of the origin of the celiac axis with some poststenotic dilatation. Study is from a patient with no abdominal complaints related to this finding.

CA narrowing has been raised by several investigators. In one study of 50 patients with no gastrointestinal symptoms who underwent abdominal angiography, 12 had CA narrowing of 50% or greater, usually with the characteristic configuration associated with compression by the median arcuate ligament or celiac ganglion. ~G Cotapinto et al. reviewed 152 routine lateral aortograms and found some CA narrowing in 74 studies and a greater than 50% stenosis in 42. 97 Sixty percent of the patients with moderate or severe stenosis had either no pain or pain that was considered to be due to other disorders; only 16% had postprandial pain.

In a more recent study by Szilagyi et al2 s 157 angiograms from three groups of patients were reviewed: (1) those in whom intestinal angina was suspected, (2) those with gastrointestinal diseases not primarily characterized by pain, and (3) those with miscellaneous diagnostic problems not involving the alimentary

77

tract. The incidence of narrowing was similar in all three groups (44%, 52.8%, 50%), but the more severe degrees of narrowing occurred most frequently in the miscellaneous group.

The surprisingly high frequency of CA narrowing among asymptomatic individuals, and the lack of close correlation between the severity of symptoms and the degree of narrowing in symptomatic patients indicate the need for considerable caution in attributing a patient's symptoms to the arterial stenosis.

PATHOPHYSIOLOGY OF PAIN.- Since the anatomic lesion form 7 ing the basis for the syndrome is narrowing of the major artery to the upper abdominal viscera, the pain has most frequently been attributed to ischemia. This concept has persisted in spite of volu- minous clinical and experimental evidence that isolated compromise of the celiac axis is almost always compensated for by collateral circulation from both the SMA and IMA. A clear demonstration of the immediate availability of adequate collaterals was supplied by Appleby 99 who, in the treatment for gastric carcinoma, excised the CA together with the origins of the left gastric, splenic and hepatic arteries with no ill effects in 13 patients. Sim- ilarly, in experiments in dogs, 50-100% constriction of the CA produced no gross or microscopic changes in the stomach, duodenum, liver or pancreas despite creation of significant pressure gradients between the CA and the aorta. '~176 Extensive experience gained since the advent of angiography has demonstrated that gradual atherosclerotic occlusion of two or even three of the major mesenteric arteries is common in asymptomatic patients. Hence, there is strong evidence that chronic and acute interruption of the CA are well tolerated if normal collaterals are present. Isch- emia due simply to diminution in celiac flow, therefore, is an unlikely explanation for the pain of the CACS.

A more complex concept of an ischemic origin of the pain impli- cates a "steal phenomenon" between the celiac and mesenteric circulations. According to one theory the collateral flow from the SMA to the celiac bed deprives the small intestine of an adequate blood supply. After eating, this deficiency is accentuated by the increased demand for blood by the small intestine producing "intestinal angina." Conversely, another theory is that increased blood flow to the small bowel after eating decreases the collateral flow to the celiac bed, producing ischemic pain in the viscera supplied by the celiac axis. Both theories are predicated on the "borrowing-lending" concept of distribution of blood flow, namely, that increasing blood flow to one segment of the vascular bed is achieved only at the expense of flow to another. ,ol

During extensive animal studies of the mesenteric circulation, 1~ we have observed that increasing blood flow to one segment of the splanchnic bed is associated with increased rather than decreased flow to the rest of the bed. Furthermore, if one major vessel is partially occluded collateral blood flow develops

78

promptly, and increased flow to either the bed of the occluded or unoccluded vessel is associated with increased flow in both beds. Only when both the SMA and the CA are partially occluded so that splanchnic arterial inflow is fixed and limited does increasing flow to one segment produce a decrease in flow to others. These observations indicate that at least under acute conditions the occurrence of a vascular steal within the splanchnic circulation is unlikely unless flow through both the celiac and mesenteric arteries is compromised. As this is not the case in most patients thought to have the CACS, the concept that the abdominal pain is the result of a form of mesenteric or celiac steal syndrome seems unlikely.

Stanley and Fry l~ have attempted to explain the pain on the basis of diminished pulsatile flow despite a normal volume flow in the distal mesenteric branches. They attribute this phenomenon to ~'excessive flow velocity of inordinately large volumes of blood coursing through the proximal SMA prior to its egress through collateral channels to the celiac arterial bed." Although this is an interesting theory, there are no experimental data to support it. These authors also have emphasized their clinical and experimental findings of reduced D-xylose absorption after a provocative meat meal as evidence that isolated CA stenosis produces intestinal ischemia. TM However, corroboration of their observations and elimination of other possible factors effecting absorption, e.g., altered motility, are required before the significance of this test is established.

Another widely accepted alternative to the ischemic explanation for the pain in CACS is that the pain arises in the celiac ganglion itself from pressure or throbbing by the compressed artery. The postprandial nature of the pain could be explained both by changes in position of the stomach and increased flow through the compressed artery. Some support for this theory is provided by several authors who obtained better results when the ganglion was excised than when only the ligament was incised.

Lastly, a less accepted explanation for the pain is that compression of the CA produces multiple small emboli to the upper abdominal organs.

THERAPY.--The most difficult aspect of the treatment of the CACS is the selection of patients for surgical relief of the compressed artery. Results of surgical procedures have varied from series to series, and no specific criteria can be well correlated with a successful outcome. In view of the continuing lack of objective evidence that stenosis of the CA produces any pathologic changes in the viscera supplied by that artery, we believe that only patients fulfilling strict criteria should be operated on. These criteria are abdominal pain, preferably related to eating, significant weight loss, an abdominal bruit and angiographic demonstration of the typical narrowed celiac axis. In a large medical center, with

79

special interests in vascular surgery and vascular disorders of the gastrointestinal tract, we have not encountered a single patient with these findings during the past 10 years.

The surgical approach to CACS varies with the surgeon's be- liefs concerning the cause of the pain. Those who believe it is ischemic emphasize the necessity for reestablishing CA blood flow. Those who believe that the pain is neurogenic emphasize the division or resection of the celiac ganglion. A practical approach includes incision of the ligament and local resection of the periar- terial portion of the celiac ganglion as an initial step. In a few' cases where a significant aorta-celiac axis pressure gradient remains, dilatation with a Fogarty balloon or arterial reconstruction may be warranted.

The CA is best approached through an upper midline incision entering the lesser sac either through the gastrocolic or gastrohe- patic ligament. The median arcuate ligament is easily incised superiorly for several millimeters and the celiac ganglionic plexus excised from the circumference of the artery. If a pressure gradient persists between the aorta and celiac axis, either direct local arterial reconstruction, reimplantation of the CA or a bypass procedure can be performed. The details of these techniques have already been discussed and good results have been reported with all ofthem.

RESULTS AND CONCLUSIONS. -- Excellent immediate results following operative decompression have been reported by most authors, but critical analysis of large series and recent long-term evaluations have tempered much of the early enthusiasm for these procedures. Contradictory results have been attributed to patient selection, poor follow-up and varying operative techniques.

In the largest study of the long-term results ofpatients treated for CACS, Evans made two pertinent observations? ~ First, although 83% of 47 patients were asymptomatic six months after operation, only 41% remained asymptomatic 3-11 years later. Moreover, of the 12 patients who were not treated surgically, 9 remained free of pain at the time of his report.

The controversy concerning CACS is a continuing one. At this time we agree with Watson and Sadikali 9~ that there are a small number of patients "with distressing abdominal pain not explained by customary diagnoses and not helped by customary management" who are relieved by some aspect of the operations performed for CA compression. If only patients fulfilling the criteria previously described are operated on, unnecessary procedures should be kept to a minimum. Detailed preoperative and postoperative angiographic, hemodynamic and metabolic evaluations should ultimately provide the answers to this puzzling entity.

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CONCLUSIONS

In 1971, in the foreword to Vascular Disorders of the Intestines, 1 Donaldson observed that "mesenteric vascular disease has, at last, come of age." The present monograph, which represents our current concepts of the recognition, diagnosis and treatment of the various forms of intestinal ischemia, reflects the enormous progress that has been made in a relatively brief period of time by physiologists, pathologists, internists, radiologists and surgeons. While much has been accomplished, much remains to be done. Although the prognosis for patients with mesenteric ischemia can be markedly improved by an aggressive approach, most patients still are not managed in this manner. A reliable rapid and noninvasive method of identifying acute intestinal ischemia remains to be developed. The frequent occurrence of chronic ischemic colitis is yet to be widely recognized, and the ischemic nature of "ulcerative colitis in the elderly" requires more extensive documentation. The validity of the test proposed for diagnosing chronic intestinal ischemia must be corroborated.

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Ischemic disorders of the intestines