Toxic Megacolon in Ulcerative Colitis

GASTROENTEROLOGY® Official Publication of the American Gastroenterological Association @ COPYRIGHT 1974 THE WILLIAMS

&

WILKINS CO.

May 1974

Vol. 66

Number 5

TOXIC MEGACOLON IN ULCERATIVE COLITIS SHELDON

C. BINDER,

M .D ., JAMES

F.

PAITERSON, M .D . , AND DONALD J . GLOTZER, M . D.

Departments of Surgery and M edicine, Tufts Univ ersity. School of Medicine and N ew England Medical Center Hospital , Boston, Massa chusetts

A consecutive series of 18 patients with toxic megacolon has been managed with a policy of early operative intervention if optimal medical therapy has failed to effect a rapid remission. One patient achieved a sustained remission on medical management alone. Seventeen patients underwent ileostomy and colectomy. There was one death (5.6% mortality rate) in a complication of ulcerative colitis in which the average reported mortality rate has been 23.1%. It is suggested that surgical intervention be used early enough to prevent colonic perforation and the progressive metabolic deterioration that prolonged nonoperative medical management may produce. The ominous prognosis of toxic megacolon and of its surgical management in the past can be overcome by resort to earlier surgical intervention. Colectomy, rather than decompressive enterostomy, is advocated as the operative treatment of choice. Toxic megacolon is a potentially lethal complication of ulcerative colitis which occurs in between 1.6 and 6% of all cases 1-4 and in 9.5 to 20% of severe attacks of ulcerative colitis. 5 The pathogenesis of this morbid dilation of the colon is unknown but has been ascribed to transmural extension of the inflammatory process with destruction of the muscularis propria and impairment of the intramural circulation of the bowel. Opiates, belladonna alka-

loids, and barium enema have been implicated etiologically as immediate precipitating factors. 5-11 In the past, the treatment of toxic megacolon has been one of prolonged nonoperative management because of the high mortality rates with operative therapy. Such treatment avoids the disadvantages of a permanent ileostomy and has effected some prolonged remissions even after long periods of little or no improvement. The risk of colonic perforation and the mortality rates of such Received November 20, 1973. Accepted January a temporizing course of therapy, however, 11, 1974. have proved too great to justify.12 Most Address requests for reprints to: Dr. J ames F. recent reports have, therefore, advocated Patterson, New England Medical Center Hospital, early operation . In many of even these 171 Harrison Avenue, Boston, Massachusetts 02111. reports, the intervals between the onset of This study was supported in part by a grant from toxic megacolon and operation have been the John A. Hartford Foundation, Inc. Dr. Glot zer's present address is: Depart ment of rather long. We have established the policy Surgery, Beth Israel Hospital, Boston, Massa- to limit ourselves to 48 to 72 hr of optimal chusetts. medical treatment, and to operate on those 909

co o '"""'

43F

32M

57F

19M

35M

69M

8

9

10

11

12

13

56M

5

19F

60M

4

7

IBM

3

25F

43M

2

6

24M

1

4yr

12.5 yr

5 yr

7wk

6yr

1 yr

6wk

3,5 yr

5wk

3wk

4mo

4mo

7mo

Duration of disease before Case Age, sex diagnosis of toxic megacolon

3mo

3 days'

2wk

7wk

9wk'

4wk

6wk'

3wk'

5wk

3wk

12 days

4mo

1mo

Duration of attack before diagnosis oftoxic megacolon

Opiates

None

None

Barium enema 1 wk before; opiates Barium enema 1 wk before; opiates

Barium enema 2 days before; opiates

Opiates, anticholinergics

None

Opiates, anticholinergics

Opiates

Barium enema 9 days before; anticholinergics Barium enema 3 wk before; anticholinergics Anticholinergics

Predisposing factors

Time of operation after diagnosis of toxic megacolon

48 hr after recurrence C

48 hr

48 hr

24 hr

48 hr after recurrence C

No operation

56 hr

72 hr

24 hr

48 hr

72 hr

5 days

None

Cecum preoperatively None

None

Walled-off cecum

None

None

None

None

None

None

None

None

Perforation of colon

Total proctocolectomy Total proctocolectomy 1 0 closure perineum Total proctocolectomy

Subtotal colectomy, Hartmann Total proctocolectomy

Subtotal colectomy, SMF Subtotal colectomy, SMF Subtotal colectomy, SMF Subtotal colectomy, SMF Subtotal colectomy, SMF

Subtotal colectomy, SMF" Total proctocolectomy

Operation performed

Transverse colon to rectum

Hepatic flexure to rectum

Total colon

Total colon

Distal sigmoid and rectumbarium enema 3 mo later Total colon

Total colon

Total colon

Total colon

Hepatic flexure to rectum

Total colon

Total colon

Total colon

Pathologic extent of involvement of colon with ulcerative colitis

Urinary retention, TUR

Marrow aplasia 2" chloromycetinsepsis, hemorrhage Pelvic abscess septicemia Perineal wound abscess

Superficial wound infection

None

None

None

None

Skin separation about ileostomy

Skin separation about ileostomy

Superficial wound infection

None

Complications

1. Toxic megacolon in ulcerative colitis: summary of our series

48 hr

TABLE

days

34

17

50

Died 7 days postoperaatively

60

17

21

30

34

60

32

31

Hospitalization postoperative

Well at 3 yr

Well at 3 yr

Wellat4yr

Proctectomy at 3 yr; well at6yr

Mild relapse at 2 yr; well at 7 yr

Proctectomy at ll12 yr; well at 7 yr

Proctectomy at 2 yr; well at 8 yr

Incisional herniorrhaphy, turn-in mucous fistula at 3 yr; well at 10 yr Proctectomy at 5 yr; well at 8 yr

Proctectomy at 6 yr; well at 11 yr

Well at 12yr

Proctectomy at 3 mo; well at 12 yr

Follow-up

.

C'>., 'iil

'"o

§'" z

"o

-0

<.>

"

Z

E

bJl::>

.S "t

".

"o

-0 <.>

E

bJl::> ~

Clinical Material

.5

".

"0 '"

"0 '"

'" 0

~~

~~

patients who have not shown objective evidence of progressive improvement within this time. To emphasize the efficacy and safety of our treatment policy, we are presenting a series of 18 consecutive patients treated in this way over the course of the past 13 years in this hospital. Colectomy, rather than various forms of emergency colonic decompression, was uniformly employed in this series of patients when operation was required. It is our intention to emphasize that this form of operative therapy can be performed safely without resorting to the temporizing and less definitive cecostomy advocated earlier by Klein and others 3 • 13-15 or the multiple "-ostomy" technique advocated more recently by Turnbull and associates. 16

'"

0

Between 1961 and 1973, 18 patients with toxic megacolon were managed at the New England Medical Center Hospital, during which interval a total of 220 patients were treated for ulcerative colitis. The data concerning these patients are summarized in table 1. Diagnosis was made by clinical examination, sigmoidoscopy, and the appearance of plain roentgenograms of the abdomen. There were 13 males and five females, with an age range from 18 to 69 years. It occurred in equal numbers of patients suffering their initial attacks of ulcerative colitis and in those having a relapse of chronic disease. Barium enema examination had been performed during the current episodes in 8 patients. Anticholinergic drugs and/or opiates had been administered in 13 cases. Hypokalemia was observed in 4 cases, but in none was its correction associated with clinical improvement of the patient. In 9 patients, toxic megacolon developed prior to admission to our hospital; in 9, it occurred during our hospitalization. All patients developed the complication during attacks which, according to the criteria of Truelove and Witts, 17 were considered severe. Although not all patients manifested leukocytosis, all had significant shift to immature forms on their differential white blood counts. All patients had varying degrees of abdominal tenderness and rebound; but in keeping with the observations of others, abd.ominal distention was frequently not consistent with the degree of colonic distention demonstrated roentgenographically.3, 7, IS The management from the outset was a joint medical and surgical venture. Nasogastric suction was instituted. Fluid, electrolyte, and 911

912

BINDER ET AL.

serum albumin deficits were corrected. Significant anemia was corrected by blood transfusion. Parenteral corticosteroids equivalent to 300 to 400 mg of hydrocortisone or adrenal corticotropin, 40 to 80 U, were administered daily. Systemic antibiotics were given in all cases. Plain X-ray films of the abdomen were taken daily or more frequently to follow the course of the colonic distention. Leukocyte counts and differential white blood cell counts were done daily. Most important, frequent clinical examinations were performed by experienced personnel. Any worsening of the condition of the patient on this program dictated immediate operation. Delay in surgical intervention beyond 48 to 72 hr was considered justified only if there was dramatic progressive improvement in signs of toxicity, abdominal distention, and tenderness and ileus, and by roentgenographic evidence of decrease in colonic distention.

Results One patient (case 8) made a complete recovery without resort to operative intervention. Two other patients (case 9 and 13) recovered for a short time before recurrence of toxic megacolon necessitated operation. Five patients were operated on without a trial of medical management because of suspected or actual perforation. Nine patients required operation because of failure to respond adequately to this nonoperative management. In only 1 case (case 11) did perforation occur during medical therapy. Subtotal colectomy, ileostomy, and sigmoid mucous fistula was performed in 7 cases; subtotal colectomy, ileostomy, and Hartmann turn-in of the rectal stump was performed in 2 cases; and total proctocolectomy with ileostomy was performed in 8 cases. The perineal wound was closed primarily in two of the seven total proctocolectomy operations; in one of these, the perineal wound had to be reopened because of sepsis. In 3 patients, the colon was found to be perforated at the time of operation; and in 2 patients the colon was perforated intraoperatively. Seven of the 10 major complications attributed directly to the operation were of septic etiology. The one death (case 10) was in large part related to bone marrow aplasia and a resultant hemorrhagic diathesis secondary to chloromycetin therapy ad-

Vol . 66, No.5

ministered for generalized sepsis. The postoperative period of hospitalization varied from 17 to 62 days, with a mean of 32 days. In follow-up evaluation, all patients who survived operation have been well for between 1 and 13 years. Of the 7 patients who underwent subtotal colectomy, 5 have undergone uneventful resection of their retained rectal stumps from 3 months to 6 years after their initial operation. The 1 patient who sustained a remission on nonoperative therapy has had only mild exacerbations of ulcerative colitis since her episode of toxic megacolon 7 years ago.

Discussion and Conclusions Our treatment policy in the management of toxic megacolon has been based on two conclusions which can be drawn from a review of the literature on this subject. The first is that colonic perforation is a common complication of toxic megacolon and carries with it a very high mortality rate. The second is that a small proportion of patients will recover from toxic megacolon with nonoperative therapy and sustain a prolonged remission; therefore, the occurrence of this complication is not an absolute indication for operation. A survey of some recent literature on toxic megacolon which supports these conclusions is presented in table 2. Of the 497 cases reviewed, only 28.9% of patients were successfully managed medically, with an over-all medical mortality rate of 30.3% and a resort to operative intervention in 40.8%. Of the patients dying under medical management, 32.6% had suffered a colonic perforation, which carried a mortality rate of 82.4% if not operated on. The corresponding surgical salvage rate has been 78.4%, but the operative mortality rate of 21.6% is alarmingly high. A substantial part of the burden of this high operative mortality should be attributed not to operation per se, but to the prolonged medical therapy preceding operative intervention. In the absence of colonic perforation, the surgical mortality rate was 8.7%; once perforation occurred, however, this rate rose to 51.2%. The mortality rate for all

May 1974 TABLE

2. Survey of literature: toxic megacolon in ulcerative colitis

Author

Year

Total cases

Lumb' . .. . . ... . .. , . . McConnell 19 .. ..... .. ... . . .. .. . . . Roth" Klein" . . .. . .......... Korelitz," Marshak" .. Peskin' . . . . ........ . Sampson21 .. . . . . . .. . . McInerney' · . .. . . . .. . Smith'· . ...... ... .. . Rowe" . ... ... . ...... Edwards' . .... . .. . . . Prohaska 23 . . .. . . . . . . . Silverberg" ... . . . .. . .. D iethelm " ... ... .... . McElwain ' · · . . . . ... . . Ferrante" .. . ... .. . .. . Neschis's . ............ Jalan' . ... · . . . . .. ... Judd, 7 Odyniec' . . . . . . Thomford 1 1 .. .. . .. . . Norland s .. .. ... . . . .. . Goligher' · .. .... .. ... Foley's . . . ...... . ..... Turnbull'S . . .. . . . . . . Collier'· .... .. . .. .. .

1955 1958 1959 1960 1960 1960 1961 1962 1962 1963 1964 1964 1964 1964 1965 1965 1968 1969 1969 1969 1969 1970 1970 1971 1971

7 26 12 3 16 9 14 36 11 10 10 16 4 6 9 6 12 55 37 23 42 28 28 42 35

Totals

. . . .. . .. .

.

913

TOXIC MEGACOLON

497

Success ful medi cal management

1 16 5 3 0 23 1 1 6 0 4 1 4 7 13 3 8 1

15 112/388 28.9%

Number ofperforations

6 4 4 0 4 7 4 10 4 5 1 9 2 0

Over-all mortality

4 6 3 0 3 2 4 10 2 1 3 5 1 0 0 0 2 25 4 6 8 5 9 2 10

1 1 ? 16 9 6 10 11 12 ? ? 126 25.4%"

115 23.1%

Medical mortality

Surgical mortality

With Without 2° per- Over-all perforaperforaOver-all foration tion tion

0 5/21 1/11 2/5 0 5/28 2/3 0 3/9 1/1 0 0 0 10/17 1/14 1/4 3/10 0

9/24

0 2/2 0/ 1

4/6 1/5 2/6 0/3 0 1/11 0 2/9 4/14 4/5 5/8 1/2 0/8 0 1/9 0 0/1 5/16 1/1 0/3 0/6 0 0/5 0 0/5 0 2/8 4/4 15/38 0 3/23 1/ 1 5/19 1/1 7/32 0 5/27 9/28 2/42 ? 1/11

4/6 0/2 1/2 0 1/4 2/7 4/6 4/5 0/3 1/5 0 5/9 0/1 0 0/1 0/1 ? 8/12 ?/9 ?/5 5/9 ? 7/9 0 ?

0 1/3 1/4 0/3 0/7 0/2 0/8 1/3 0/5 0/4 0/1 0/7 0/2 0/6 0/4 0/4 ? 7/26 ?/14 ?/14 1/23 ? 2/19 2/42 ?

43/142 14/17 74/343 42/82 15/173 30.3%" 82.4% 21.6% 51.2%" 8.7%

The mortahty rate for all perforatIons was 56/99, or 56.6%. "Of the 43 deaths under medical management, 14 were 2° perforation, or 32.6%. a

perforations was 56.6%. Since perforation is the most important incriminating factor in the high mortality associated with toxic megacolon, it is obvious that the keystone to successful management is the avoidance of colonic perforation. The frequency of perforations, and, consequently, the over-all mortality rates are highest in those series in which protracted medical management has been the practice. Obviously, if there is any evidence of perforation, surgery should be performed immediately. In the absence of evidence of perforation, a short period of medical management is justified to allow repletion of deficits and optimal preparation of the patient for operation. In our series, a period

of 48 to 72 hr did not adversely affect mortality and produced one sustained remission without operative intervention. A possible valid criticism of early operation is the consideration of whether any patients were subjected to unnecessary colectomy. It is difficult to ascertain how many patients managed without recourse to operation will eventually require colectomy. Goligher et a1. 29,31 . 32 were able, by operating on all severe attacks of ulcerative colitis which did not remit during a 5- to 7-day course of intensive medical therapy, to reduce the over-all mortality rate from 11.3%, when there was a 12- to 17 -day delay, to 3.7%. The medical mortality was reduced from 4.8 to 0.7%, and the incidence

914

BINDER ET AL.

Vol. 66, No.5

of colonic perforation, from 32.5 to 11.1%, lon, and that the less definitive procedures without significantly decreasing the num- advocated by others may be only a tempober of spontaneous remissions. The few rizing compromise at best. patients who were likely to secure remisREFERENCES sion of their severe attack of ulcerative 1. Edwards FC , Truelove SC: The course and progcolitis were not, in their series, deprived of nosis of ulcerative colitis. Gut 5:1-14, 1964 the opportunity to do so because operation was performed earlier. Furthermore, they 2. Lumb G, Protheroe HB, Ramsay GS: Ulcerative colitis with dilatation of the colon. Br J Surg found that 37.1% of those who survived 43:182-188, 1955 without operation during a severe attack of 3. McInerney GT, Sauer WG, Baggenstoss AH, et ulcerative colitis subsequently came to al: Fulminating ulcerative colitis with marked elective or urgent operation; and an addicolonic dilatation: A clinicopathologic study. tional 3.6% died of their disease. It is Gastroenterology 42:244-256, 1962 important to note that the series was not 4. Peskin GW, Davis AVO: Acute fulminating ulcerative colitis with colonic distension. Surg Gynecol one exclusively of patients with toxic megObstet 110:269-276, 1960 acolon but consisted of all patients with severe attacks of ulcerative colitis. Fur- 5. Jalan KN, Sircus W, Card WI, et al: An experience of ulcerative colitis I. Toxic dilatation in 55 thermore, treatment regimens were not cases. Gastroenterology 55:68-82, 1969 randomized; and the two groups of patients 6. Garrett JM, Sauer WG, Moertel CG: Colonic were studied during different periods of motility in ulcerative colitis after opiate administime. tration . Gastroenterology 53:93-100, 1967 When operation was performed in our 7. Judd ES : Current surgical aspects of toxic megaseries, no procedure other than total or colon. Surgery 65:401-406, 1969 subtotal colectomy was done. We have had 8. Norland CC, Kirsner JB: Toxic dilatation of colon (toxic megacolon): etiology, treatment and progno personal experience with tube cecosnosis in 42 patients. Medicine 48:229-250, 1969 tomy or ileostomy and multiple decompressive colostomies as advocated respec- 9. Odyniec AN, Judd ES, Sauer WG: Toxic megacolon. Significant improvement in surgical managetively by Klein et a1. 13 and Turnbull et a1. 16 ment. Arch Surg 94:638-642, 1967 The authors of this report have some differ- 10. Smith FW, Law DH, Nicker WF, et al: Fulminant ence of opinion concerning the optimal ulcerative colitis with toxic dilatation of the type of colectomy. One of the surgical colon: medical and surgical management of authors (D. J. G.) preferred subtotal coleceleven cases with observations regarding etiology. tomy since this operation proved adequate Gastroenterology 42:233-243, 1962 to relieve the toxicity of the disease and 11. Thomford NR, Rybak JJ, Pace WG: Toxic megacolon. Surg Gynecol Obstet 128:21-26, 1969 reduced the operating time in these critically ill patients. He did not find the 12. DeDombal FT, Watts JMcK, Watkinson G, et al: Intraperitoneal perforation of the colon in ulceraretention of the rectal stump to signifitive colitis. Proc R Soc Med 58:713-715, 1965 cantly increase postoperative morbidity. 13. Klein SH, Edelman S, Kirschner PA, et al: The other surgical author (S. C. B.) preEmergency cecostomy in ulcerative colitis with ferred total proctocolectomy except in paacute toxic dilatation. Surgery 47:399-407, 1960 tients with preoperative colonic perfora- 14. Korelitz El, Janowitz HD: Dilatation of the colon, tion. He found that this operation did not a serious complication of ulcerative colitis. Ann increase the operative mortality or morbidIntern Med 53 :153- 163, 1960 ity and spared the patients the necessity of 15. Marshak RH, Korelitz El, Klein SH, et al: Toxic dilatation of the colon in the course of ulcerative a future major operation to remove the colitis. Gastroenterology 38: 165-180, 1960 rectal stump. The superiority of one or the other type of colectomy cannot be deter- 16. Turnbull RB , Hawk WA, Weakley FL: Surgical treatment of toxic megacolon. Ileostomy and mined by this study, since the only postopcolostomy to prepare patient for colectomy . Am J erative fatality could not be ascribed to the Surg 122:325-331, 1971 operative procedure selected. Our study 17. Truelove SC, Witts LJ: Cortisone in ulcerative does demonstrate, however, that colectomy colitis. Br Med J 2:1041-1043, 1955 can be safely performed for toxic megaco- 18. Foley WJ, Coon, WW, Bonfield RE: Toxic mega-

May 1974

19.

20.

21. 22. 23.

24.

25.

TOXIC MEGACOLON

colon in acute fulminant ulcerative colitis. Am J Surg 120:769-774, 1970 McConnell F, Hanelin J, Robbins LL: Plain film diagnosis offulminating ulcerative colitis. Radiology 71:674-681, 1958 Roth JLA, Valdes-Dapena A, Stein GN, et al: Toxic megacolon in ulcerative colitis. Gastroenterology 37:239-255, 1959 Sampson P, Walker FC: Dilatation of the colon in ulcerative colitis. Br Med J 2:1119-1123, 1961 Rowe RJ: Dilatation of the colon (toxic megacolon) in acute fulminating ulcerative colitis. Dis Colon Rectum 6:23-36, 1963 Prohaska JV, Greer D, Ryan JF: Acute dilatation of the colon in ulcerative colitis. Arch Surg 89:24-30, 1964 Silverberg D, Rogers AG: Toxic megacolon in ulcerative colitis. Can Med Assoc J 90:357-363, 1964 Ditthelm AG, Sleisenger MH, Nicker WF: Primary resection in acute fulminating ulcerative colitis. Arch Surg 88:389-396, 1964

915

26. McElwain JW, Alexander RM, MacLean MD: Toxic dilatation of the colon in acute ulcerative colitis. Arch Surg 90:133-138, 1965 27. Ferrante WA, Egger J: Toxic megacolon complicating chronic ulcerative colitis. South Med J 58:969-973, 1965 28. Neschis M, Siegelman SS, Parker JG: Diagnosis and management of the megacolon of ulcerative colitis. Gastroenterology 55:251-259, 1968 29. Goligher JC, DeDombal FT, Graham HG, et al: Early surgery in the management of severe ulcerative colitis. Br Med J 3:193-195, 1967 30. Collier RL, Wylie JH, Gomez J: Toxic megacolon. A surgical disease. Am J Surg 121:283-288, 1971 31. Watts JMcK, DeDombal FT, Watkinson G, et al: Early course of ulcerative colitis. Gut 7:16-31, 1966 32. Goligher JC, Hoffman DC, DeDombal FT: Surgical treatment of severe attacks of ulcerative colitis, with special reference to the advantages of early operation. Br Med J 4:703-706, 1970