Imtwoved Outcome bv Identification of &h*Risk Nonoccl&ive Mesenteric Ischemia, Aggressive Reexploration,

and Delayed Anastomosis David Ward, MD, Anthony M. Vernava, MD, Donald L. Kaminski, MD, Tina Ure, MD, Gary Peterson, MD,

Paul Garvin, MD, Todd W. Arends, MD, Walter E. Longo, MD, St. Louis, Missouri

BACKGROUND: The factors associated with out- come of patients with nonocclusive mesenteric ischemia are poorly defined.

wETHoDs: Over a 7-year period, 34 consecutive patients with nonocclusive mesenteric ischemia were identified.

RESULTS: The mean age of the study patients was 63 years (range 31 to 94); 21 of 34 (62%) were men. The mean delay in diagnosis was 31 hours (range 7 hours to 6 days). Seven of 34 (21%) underwent preoperative visceral arteriogra- phy. Two of these 7 required surgery, and both dii as a result of intestinal infarction. The re- malning 27 had the diagnosis made at celiotomy. Among the 29 who were explored, 16 of 29 (55%) had intestinal infarction. Twentyone of 29 (72%) had segmentel bowel injury whereas 8 of 29 (28%) had massive injury. Among those with seg- mental infarMon, primary anastomosis was per- formed in 12 of 21 patients (57%); 5 of the 12 (42%) died. Nine of 21 patients (43%) underwent delayed anastomosis; 2 of the 9 (22%) died. No patlent with massive injury underwent primary anastomosis. Second&ok laoarotomy ws per- formed on 22 of 29 (76%). Eleven of those 22 (59%) had a further bowl resection. Overall, 16 of 29 (55%) who UnderweM surgery for nonocclu- sive mesenWic ischemia are alive.

cor4c~woNs: Improved survival from nonocclu- sive mesenteric &hernia is dependent upon the identificatbn of high-risk groups, aggressive re- exploration, and delayed intestinal anastomosis. Am J Surg. 1995;170:577-581.

S yndromes of acute mesenteric ischemia are uncommon but highly lethal disease entities and involve occlu- sion by either thrombosis or embolus of the superior

mesenteric artery, mesenteric venous thrombosis, or non-

From the Department of Surgery, St. Louis University School of Medicine, St. Louis, Missouri.

Requests for reprints should be addressed to Walter E. Longo, MD, 3635 Vii Avenue, P.O. Box 1320, St. Louis, Missouri 63110-0250.

Presented at the 47th Annual Meeting of the Southwestern Surgical Congress, April 23-26, 1995, San Antonio, Texas.

I

occlusive mesenteric ischemia. Nonocclusive mesenteric is- chemia is common but is the least understood form of mesen- teric ischemia, and vasoconstriction with loss of local auto- regulatory control mechanisms within the gut results in &hernia. This vasoconstriction is a consequence of a variety of disease entities and medications that affect the splanchnic circulation. Its true prevalence is unknown; however, a de- clining incidence is apparent and has most probably resulted primarily from improved treatment of critically ill patients, including aggressive hemodynamic monitoring and advances in pharmacotherapy for congestive heart failure and cardio- genie shock. l

Despite improvements in diagnostic modalities and care of the critically ill, the mortality of nonocclusive mesenteric ischemia in most series is substantial, with the cause of death in most cases being irreversible shock or advanced intesti- nal necrosis. This high mortality is a reflection of the fail- ure to recognize the syndrome in an earlier, treatable phase.’ In an effort to fully appreciate the spectrum of disease and its natural history, we sought to evaluate risk factors, results of selective management, and outcome of patients with nonocclusive mesenteric ischemia at St. Louis University Medical Center.

METHODS The records of all patients with the diagnosis of vascular

insufficiency of the intestine managed by the medical and surgical services at St. Louis University School of Medicine between 1987 and 1994 were reviewed. Patients with acute mesenteric ischemia secondary to either arterial thrombotic disease, arterial embolic disease, chronic visceral ischemia, mesenteric venous thrombosis, and ischemic colitis were ex- cluded. Nonocclusive. mesenteric &hernia was diagnosed when the mesenteric vessels were patent with no small-ves- sel disease evident on histology. Patients were reviewed as to age, sex, presenting symptoms, physical findings, comor- bid medical conditions including recent surgery, method of diagnosis including laboratory and radiologic findings, delay in diagnosis, results of treatment, and outcome. The extent of bowel involvement was evaluated at the primary opera- tion, and the patients were divided into those with segmental or massive bowel injury. We entered all data into a com- puterized data base. Statistical analysis of the entered data was performed using Student’s unpaired t-test to evaluate in- dividual variables. Statistical significance for each test was set at a probability of P ~0.05.

THE AMERICAN JOURNAL OF SURGERY’= VOLUME 170 DECEMBER 1995 577

UPROVED OUTCOME OF MESENTERIC ISCHEMIAIWARD ET AL

TABLE I

Event Precipitating Nonocclusive Mesenteric lschemia in 34 Patients

Precipitating Event Number of Patients %

Cardiac dysfunction 12 35 Intravascular volume depletion 8 24 Recent surgery 7 21 Transplantation 4 12 Uremia 1 3 Cocaine use 1 3 Unknown cause 1 3

TABLE II

Results of Laparotomy for 29 Patients’

Segmental infarction Resection and anastomosis: 12 patients; 5 (42%) died Resection and delayed anastomosis: 9 patients; 2 (22%) died

Massive infarction Resection and delayed anastomosis: 8 patients; 6 (75%) died

‘Includes 2 patients who failed papaverine therapy.

RESULTS Patients

Thirty-four patients with nonocclusive mesenteric is- chemia were identified. The mean age was 63 years (range 31 to 94). There were 21 men and 13 women. Physical ex- amination revealed abdominal distention in 32 patients and abdominal tenderness in 29 patients. Occult blood in the stool was found in 31 patients, and 3 patients passed me- lena. Twenty-seven patients had systemic signs with either fever (9 patients) or tachycardia (12 patients). Eight patients presented in shock. A number of precipitating factors felt to contribute to nonocclusive mesenteric ischemia were iden- tified (Table I).

Investigations The mean serum white blood cell count was 14,700 cells/mm3

(range 2,000 to 39,000), and was elevated in 28 of 34 pa- tients (82%). Metabolic acidosis was present in 14 patients. Serum inorganic phosphate was elevated in only 9 patients. Serum amylase was determined in 20 patients (59%) and was elevated in 9 (45%). All patients had plain abdominal roent- genograms made; a suggestion of intestinal ischemia was re- ported in 17 (50%). Preoperative angiography was performed in 7 patients, in whom nonocclusive mesenteric ischemia was deduced based on spasm of the mesenteric circulation in the distribution of the superior mesenteric artery. The remaining 27 patients had the diagnosis made at laparotomy. The di- agnosis was confirmed by the presence of a palpable pulse in the superior mesenteric artery and the absence of mesenteric venous thrombosis during resection, and when the mesen- teric vessels were patent with no small-vessel disease evident on histology. The mean delay in diagnosis was 31 hours (range 7 hours to 6 days).

Treatment All 7 patients who were diagnosed angiographically were

given intra-arterial papaverine. Radiographic resolution of

arterial spasm was confirmed in 7 patients. Five of the 7 pa- tients were treated successfully without surgery. Two of the 7 patients developed continued abdominal pain and clinical deterioration requiring laparotomy and bowel resection. The remaining 27 patients were diagnosed at laparotomy after being felt to have a surgical abdomen. In 11 of 27 patients, the diagnosis of acute mesenteric ischemia was entertained but arteriography was foregone because of peritonitis. The remaining 16 patients were felt to have a surgical abdomen on the basis of other surgical conditions. Among these 27 patients, 14 were found to have evidence of frank intestinal infarction with gangrene of the involved segment, whereas the remaining had clearly ischemic but not gangrenous in- testine. Twenty-one of 29 (7.2%) had segmental injury whereas 8 of 29 had massive injury.

Overall Outcome Among the 2 1 patients with segmental injury, 12 of 2 1(57%)

underwent resection and primary anastomosis (Table II). The mean amount of small intestine removed was 28 cm. Four of 12 patients developed anastomotic leaks requiring re- resection and a stoma. In all 4 patients, further intestinal is- chemia was present. Eight of 12 underwent a second-look Ia- parotomy, and 5 were found to have further intestinal ischemia. Seven of 12 patients (58%) who underwent resec- tion and primary anastomosis are currently alive. The cause of death among 5 of 12 patients was sepsis and multiple or- gan failure from intestinal infarction. Among those patients who survived, the mean hospitalization time was 33.2 days. Nine of 2 1 patients with segmental injury were treated by re- section and end stoma. This decision was based on the sur- geon’s discretion with respect to hemodynamic instability and coexisting patient morbidity. The mean amount of small in- testine removed was 41 cm. Six of 9 patients underwent a second-look laparotomy, and 3 were found to have further intestinal ischemia. Seven of 9 patients (78%) who under- went resection and end stoma are currently alive. One pa- tient died from sepsis and multiple organ failure from in- testinal infarction and the other died from a myocardial infarction on postoperative day 21 while eating a regular diet. Among patients who survived, the mean hospitalization was 33.2 days.

Among the 8 patients with massive bowel injury, all un- derwent resection and end stoma. The mean amount of small intestine removed was 118 cm. Seven of 8 underwent a sec- ond-look laparotomy, during which further ischemia was found in 3. Six of 8 (75%) patients with massive bowel in- jury died. The cause of death for all 6 was sepsis from in- testinal infarction. For the 2 patients who survived, the mean hospitalization was 79.5 days. Both patients remain ventila- tor-dependent in chronic care facilities.

COMMENTS Nonocclusive mesenteric ischemia is the result of splanch-

nit vasoconstriction in response to a number of systemic in- sults that result in a reduction of mesenteric blood flow. Many of these patients have had recent myocardial infarction, are in congestive heart failure, are hypovolemic, and are currently taking medications that are known to reduce splanchnic blood flow. Other patients who are at risk are those with drug

578 THE AMERICAN JOURNAL OF SURGERY@ VOLUME 170 DECEMBER 1995

IMPROVED OUTCOME OF MESENTERIC ISCHEMWWARD ET AL 1

intoxication in response to cyclosporine, propranolol and

phenobarbital overdosage, use of ergot derivatives, cocaine

ingestion, after repair of aortic coarctations, and with renal

failure and various other shock states.?-’ Nonocclusive mesen-

teric ischemia has also been described after cardiopulmonary

bypass and is associated with both a significant delay in di-

agnosis and substantial mortality.‘@ Diuretic agents have also

been implicated in the etiology of nonocclusive mesenteric

ischemia, although it is uncertain whether this is simply the

result of volume contraction or whether there is a direct ef-

fect on the mesenteric vasculature mediated via either the

renin-angiotensin system or antidiuretic hormone.” Patients

with end-stage renal insufficiency on hemodialysis also repre-

sent a high-risk group for development of nonocclusive mesen-

teric ischemia, which is felt to he related to underlying ath-

erosclerosis, uremic microangiopathy, and dialysis-associated

hypotension.”

Prompt recognition and early therapeutic intervention are

crucial to the successful management of patients with nonoc-

elusive mesenteric ischemia. Brandt and Boley13 stressed that

patients at risk must be identified. These are usually elderly

persons with congestive heart failure, cardiac arrhythmias,

recent myocardial infarction, hypovolemia, hypotension, or

sepsis. Furthermore, abdominal pain, which may not be pres-

ent, may be out of proportion to the abdominal findings early

in the course of ischemia. Abdominal distention, gastroin-

testinal bleeding, or an unexplained abdominal illness may

be the only indication of intestinal ischemia. When abdom-

inal tenderness, fever, vomiting, bowel obstruction, or shock

appear, irreversible intestinal infarction has probably already

occurred. Leukocytosis, metabolic acidosis, hyperamylase-

mia, and hyperphosphatemia are usually late findings and

should alert one to the presence of intestinal necrosis. Failure

to proceed with angiography during this critical period be-

fore bowel infarction is related to a high mortality.

Initial treatment should address correction of any underly-

ing cause, such as relief of congestive heart failure, treatment

of arrhythmias, or correction of hypovolemia. Digitalis and

vasopressors should be discontinued or avoided if at all pos-

sible. A broad-spectrum intravenous antibiotic should be ad-

ministered to all patients in whom the diagnosis of nonoc-

elusive mesenteric ischemia is entertained. A Swan-Ganz

catheter should be placed. Plain abdominal radiographs

should be obtained to exclude the presence of an alternate

diagnosis. If the plain films fail to show another cause for the

pain, immediate angiography should be performed. The an- giographic pattern of nonocclusive mesenteric ischemia re-

veals narrowing at the origins of major superior mesenteric

artery branches, irregularities of major branches with alter-

nating dilation and constriction, spasm of peripheral arcades,

and impaired filling of intramural vessels.14 In addition to the

above findings, delayed arterial emptying of mesenteric veins

may also be associated with ischemia. Once the diagnosis is

confirmed, an intra-arterial infusion of papaverine is begun

through the catheter in the superior mesenteric artery.14 A

constant rate of 30 to 60 mg per hour is maintained. If per-

sistent peritoneal signs are present, the patient is taken to the

operating room where the infusion is continued during and

after laparotomy. The infusion is continued for 24 hours, and angiography is repeated 30 minutes after changing the infu-

sion to saline. Based on the angiographic response of the vaso-

constriction and the patient’s clinical course, the infusion is

either stopped or continued for another 24 hours, at which

time the situation is similarly reevaluated. When papaverine

is used in conjunction with laparotomy, the infusion is con-

tinued postoperatively and stopped only when vasoconstric- tion has angiographically resolved and the patient’s abdom-

inal findings have normalized. We stress that the decision

about a second-look operation should be made prior to the

patient leaving the operating room.

Recent reports of outcome of patients with nonocclusive

mesenteric ischemta have been few. Boley et alI5 reported

their results with 15 patients with nonocclusive mesenteric

ischemia. Five patients without peritoneal signs responded

well and survived without operation. Two patients with peri-

toneal signs responded to papaverine infusion alone and did

not require laparotomy. Seven patients with peritoneal signs

underwent laparotomy; 5 underwent resection of gangrenous

bowel, and 2 of these survived. The other 2 patients with

peritoneal signs had segments of gangrenous bowel deemed

too extensive for resection. One patient with peritoneal signs

died before the operation was performed. The presence of

peritoneal signs was predictive of a poor outcome. Clark and

Gallanti reported on 11 patients with nonocclusive mesen-

teric ischemia. Three had irreversible vasoconstriction with

injection of vasodilator; all 3 died with segments of infarcted

bowel noted at surgery or autopsy. Eight patients had revers-

ible vasoconstriction angiographically; 7 received intra-

arterial papaverine infusions and 1 received intra-arterial

prostaglandin E. Five patients underwent exploratory lapa-

rotomy 24 to 48 hours after vasodilator therapy, and all sur-

vived without bowel resection. Three other patients receiv-

ing papaverine subsequently developed necrotic bowel, and

all 3 died. The overall survival rate for patients with nonoc-

elusive mesenteric ischemia was 45%. Sachs et ali7 identi-

fied 7 patients with nonocclusive mesenteric ischemia; 6 of

these pattents had peritoneal signs and were treated by a

combination of bowel resection and vasodilator therapy. Five

of the 7 patients died (71%).

Our retrospective analysis of patients with acute mesen-

teric ischemia without demonstrable evidence of acute ar-

terial or venous occlusion has demonstrated that improved

survival can be expected with the early identification of

high-risk groups, aggressive reexploration for suspected pro-

gression of intestinal ischemia, and delaying intestinal anas-

tomosis until a subsequent hospitalization. Nevertheless, as

in other series, this disease still results in a significant mor-

tality, especially in the presence of intestinal infarction. Our

data do, however, demonstrate that the diagnosis is often

not considered preoperatively, and nearly 50”/0 of patients

had both an alternative diagnosis considered preoperatively

and an intestinal infarction found at the time of laparotomy.

Nevertheless, despite a wide range of negative examinations

in critically ill high-risk patients, emergency angiography of at-risk patients with persistent abdominal pain will allow for

nonocclusive mesenteric ischemia to be diagrnosed at a cur-

able stage. Delayed intestinal anastomosis and aggressive re-

exploration will allow for the local effects of the systemic in-

sult causing nonocclusive mesenteric ischemia, which may persist for a longer period of time, to abate and eliminate

J THE AMERICAN JOURNAL OF SURGERY@ VOLUME 170 DECEMBER 1995 579

the possibility of further ischemia or anastomotic breakdown that will add to the already significant mortality rate.

REFERENCES I. Rivers SP, Vieth Fj. Non-occlusive mesenteric ischemia. In:

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2. Hildebrandt HD, Zierler RE. Mesenteric vascular disease. Am_J Surg.

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3. Halldorsson A, Hunter GC, Zukoski CF, et al. The possible role of

cyclosporine in non-occlusive mesenteric ischemia in a renal trans-

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4. Pettei MJ, Levy J, Abramson S. Non-occlusive mesenteric ischemia

associated with propranolol overdose: implications regarding splanch-

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5. Olson KR, Pond SM, Vernier ED, et al. Intestinal infarction com-

plicating phenobarbital overdose. Arch Intmn Med. 1984;144:407+08.

6. Kawauchi M, Tada Y, Asano K, et al. Angiographic demonstration

of mesenteric arterial changes in postcoartectomy syndrome. Surgery.

1985;98:602.

7. Valentine RJ, Whelan TV, Meyers HF. Nonocclusive mesenteric

&hernia in renal patients: recognition and prevention of intestinal

gangrene. Am J Kidney Dis. 1990;15:59&600.

8. Greene FL, Ariyan S, Stansel HC Jr. Mesenteric and peripheral

vascular ischemia secondary to ergotism. Surgery. 1977;81:176.

9. Nalbandian H, Sheth N, Dietrich R, et al. Intestinal ischemia caused

by cocaine ingestion: report of two cases. Surgery. 1985;97:374.

10. Allen KB, Salam AA, Lumsden AB. Acute mesenteric ischemia

after cardiopulmonary bypass. J Vast Surg. 1992;16:391-396.

11. Arends T. Nonocclusive mesenteric ischemia. Setnin Colon Rectal

Surg. 1993;4:212-217.

12. Engel A, Adler OB, Loberant N, et al. Nonocclusive ischemic

bowel disease in patients on chronic hemodialysis. Fort.& Runtgenstr.

1989;150:704-707.

13. Brandt LJ, Boley SJ. Nonocclusive mesenteric ischemia. Ann Rew

Med. 1991;42:107-117.

14. Siegelman SS, Sprayregen S, Boley SJ. Angiographic diagnosis of

mesenteric arterial vasoconstriction. Radiobgy. 1974;112:533-542.

15. Boley SJ, Sprayregen S, Siegelman SS, et al. Initial results from

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teric ischemia. Surgery. 1977;82:848-855.

16. Clark RA, Gallant TE. Acute mesenteric ischemia: angiographic

spectrum. Am J Roentgend. 1984;142:555-562. 17. Sachs SM, Morton JH, Schwartz SI. Acute mesenteric ischemia.

Surgery. 1982;92:646.

DISCUSSION James Thomas, MD (Kansas City, Kansas): This is a very

timely topic, particularly since the authors have demon- strated in their study that the incidence of nonocclusive mesenteric ischemia is decreasing. This makes the diagnosis much more difficult for those of us who see these patients with abdominal pain in the intensive care unit and other ar- eas. This is confirmed by the fact that only 7 of this group of patients underwent angiography. Clearly, angiography plays a major role in the diagnosis, and since the diagnosis is extremely difficult, angiography was not applied gener- ously in this particular group of patients.

The data presented by Dr. Long0 are collected in a retro- spective manner. I think this is a critical presentation and a critical subject, however, so the retrospective nature of analy- sis should not be considered. It has been suggested that de- laying intestinal anastomosis will improve outcome. In fact, I think 80% of those patients survived, in contrast to only

IMPROVED OUTCOME%f

60% of those patients who underwent primary anastomosis. These are relatively small numbers, but the P values are quite good even though the numbers were relatively small.

I have a number of questions for Dr. Longo. First, did you identify high-risk groups? You make a point that we can de- crease the overall morbidity and mortality of this problem if we can identify those people who are at risk for developing nonocclusive mesenteric vascular disease. I would like you to comment on the character of those individuals who are at risk.

Second, you used the second-look operation fairly routinely in 22 out of 29 patients. Is there any way that you might avoid using the second-look operation by intraoperative as- sessment by some technique of the viability of bowel? And finally, how did you decide to use stomas in this particular group of patients?

Kevin Thomas, MD (Wichita Falls, Texas): I wondered whether acute abdominal compartment syndrome may be an etiology since it has been observed in trauma patients, and wondered if there might be a way of measuring intra-abdom- inal pressures in a prospective manner with this problem?

CLOSING Walter E. Longo, MD: Dr. Thomas, the high-risk group of

patients are really not any different than they were 10 or 15 years ago. We are clearly operating on more elderly, debili- tated patients than we ever had in the past, so this elderly pop- ulation remains a high-risk group. Patients with cardiac dys- function are another high-risk group. Penetrating trauma remains a large group of patients that we see. A number of our patients that were operated on were patients who had previ- ous trauma, either orthopedic trauma or neurological injuries. The patients who undergo cardiopulmonary bypass-espe- cially extended procedures where four, five, or six vein grafts are done at the same time along with cardiac valvular proce- dures-are another group of patients who have a high risk for developing midgut nonocclusive ischemia. Transplant patients also, especially those who undergo liver transplant or pancre- atic transplant, is another group of high-risk patients that we saw. Of course, there are the patients who use drugs either recreationally or nonrecreationally. In the transplant group of patients, 2 of our 4 patients had cyclosporine toxicity.

With regard to intraoperative assessment, a number of tech- niques are used for intraoperative assessment. This includes clinical judgment, intravascular dyes, and duplex ultrasound scanning. Studies that compare clinical judgment with these other techniques have shown that with this group of patients the surgeon is, if anything, not underaggressive but over- aggressive and would normally be resecting more bowel than he should based on clinical assessment. So clinical judgment remains fairly unreliable as far as determining the patient’s intestinal viability. The other techniquesintravascular dyes and duplex scans--are the ones we mostly use. Most physi- cians are more familiar with these. They are also cost effec- tive. We use a combination of fluorescein with laser Doppler velocitometry when we have that available. Other tech- niques, such as surface tension and infrared photoplethys- mography, we have no experience with.

The decision about intestinal anastomosis is always a diffi- cult one. My personal feeling is that compared with occlu- sive ischemia where the genesis of the problem is readily ev-

580 THE AMERICAN JOURNAL OF SURGERYa VOLUME 170 DECEMBER 1995

1 IMPROVED OUTCOME OF MESENTERIC ISCHEMWWARD ET Al

ident, either a thrombus or an embolus, you are restoring blood flow to the gut of these patients and you’ve pretty much taken care of the problem. Nonocclusive &hernia remains an enigma. Even though you do correct the patient’s cardiac output and increase mesenteric perfusion pressure, these pa- tients are prohably at risk for continued mesenteric ischemia 2, 3, 4, 5 days after, because of alterations in the renin-an- giotensin system, liberation of secondary mediators of in- flammation such as thromboxanes, leukotrienes, and platelet- activating factor, all of which have inherent vasoconstrictive properties. So for this group of patients with nonocclusive is- chemia, you’re not sure whether their perfusion is adequate to maintain an anastomosis, because the genesis of the insult

isn’t well defined. This is why I have a low threshold for not doing an anastomosis and doing a stoma.

With regard to the decision at the time of laparotomy for patients who have just one small segment of ischemia, I would feel comfortable going ahead and doing an anastomosis in that group of patients. However, patients who have multiple segmental disease, patients who have massive ischemia or in- farction, and patients in whom the transition zone from is- chemia bowel to nonischemic bowel is not appreciated- these are other groups of patients for whom I would not favor an anastomosis and would favor doing a stoma.

Finally, as for techniques for measuring intraabdominal pressure, I’m not familiar with any of these.

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