An Experience of Ulcerative Colitis

An Experience of Ulcerative Colitis

Vol. 57, No.1 Printed in U.S.A. GASTROENT EROLOGY Copyright © 1969 by The Williams & Wilkins Co. AN EXPERIENCE OF ULCERATIVE COLITIS I. Toxic dilat...

8MB Sizes 0 Downloads 110 Views

Vol. 57, No.1 Printed in U.S.A.

GASTROENT EROLOGY

Copyright © 1969 by The Williams & Wilkins Co.

AN EXPERIENCE OF ULCERATIVE COLITIS I. Toxic dilation in 55 cases K. N. JALAN, M.B., B.S., W. Smcus, M.D., PH .D., W. I. CARD, M.D., C. W. A. FALCONER, M.B. , CH.B., J . BRucE, D.Sc., G. P. CREAN, M.B., B.CH., PH.D. , J.P. A. McMANus, M.B., CH.B., W. P. SMALL, V.R.D ., CH.B., CH.M., AND A. N. SMITH, M.D . Gastro-Intestinal Unit, Western General Hospital, Edinburgh, Scotland; and the Department of Medicine in Relation to Mathematics and Computing, Univ~rsity of Glasgow, and Southern General Hospital, Glasgow , Scotland

A series of 55 cases of toxic dilation occurring in a group of 399 cases of ulcerative colitis is described. "Toxic dilation" of the colon in ulcerative colitis., is shown to result in a high mortality. Perforation of the colon, massive hemorrhage and bacteremia are more common than in colitis without dilation and adversely affect prognosis. Therefore, it is imperative to find ways for the early recognition of cases at risk. The outcome appears to be modified by sex, the length of history of the disease, and the duration of the present attack, but is not significantly influenced by age, extent of involvement of the colon, mode of onset, or whether the complication appears in a first attack or relapse. Prognosis has improved since the introduction of intensive care including corticosteroids and protein replacement, but deterioration and death still occurred in more than one-third. Most of the patients treated conservatively who died did so within 10 days. For this reason, a policy is recommended that, once the complication has been recognized, surgery be undertaken with the minimum of delay. litis reveals that this complication is not always clearly defined and examples of it are usually included in case groups labeled "acute fulminating ulcerative coli-

For the purposes of this survey, "toxic dilation" of the colon is defined as total or segmental colonic dilation occurring in a severe attack of ulcerative colitis. A review of the literature on ulcerative co-

. " t IS.

Colonic dilation is recognized as a potentially lethal complication of severe colitis. The results of treatment, in relation to both mortality and morbidity, remain far from satisfactory even though the outlook has improved with better understanding of electrolyte, fluid , and protein requirements; with the introduction of corticosteroids; and with the acceptance of the concept of early surgery in selected cases. The management still presents formidable problems to both physician and surgeon. Isolated examples of toxic dilation are

Received December 16, 1968. Accepted February 18, 1969. The results of part of this survey were reported to the British Society of Gastroenterology at their Annual General Meeting held in Dublin, Ireland, in November 1967. Address requests for reprints to: Dr. W. Sircus, Gastro-Intestinal Unit, Western General Hospital, Crewe Road, Edinburgh 4, Scotland. Dr. Jalan was supported by a grant from the Scottish Hospitals Endowment Research Trust. Dr. Sircus is an External Member of Staff of the Medical Research Council. The authors are grateful to Mrs. S. Burford for technical assistance. 68

July 1969

69

AN EXPERIENCE OF ULCERATIVE COLITIS

found in reports of single cases of colitis T ABLE 1. Criteria of diagno sis (retr ospective from the Massachusetts General Hospital analysis) in 1933, 1936, and 1941 and since by others. 1-6 Madison and Bargen' first drew 1. Evidence of dilation Clinical: visible abdominal distension and/or attention to it in their report. Lumb and peritonism (rebound tenderness) 8 his colleagues discussing the pathological Radiological: segmental or to tal colonic disfeatures laid particular stress on transtension with or without pseudopolypi mural extension of the inflammation. 9 Bockus et al. used the term "toxic agan- 2. Evidence of toxicity glionic megacolon" and suggested that the Pyrexia > 101.5 F Tachycardia > 120 per min pathogenesis "may depend upon destrucLeucocytosis > 10,500 per cu mm tive changes in the nerve plexus of disAnemia-hemoglobin < 60% eased colon particularly the myenteric plexus." Dehydration Series of cases dealing with various Mental changes aspects of this syndrome have been reElectrolyte disturbance ported by several observers in the last 8 Hypobension years. t o - t 5 In this retrospective study the findings 3. Subsequent pathological confirmation of dilaare evaluated in 55 patients admitted tion and t ransmural extension of the inflammatory process with this complication to a gastrointestinal unit offering combined medical and surgical care. TABLE

Material and Methods Criteria. In the course of a review of 399 cases of ulcerative colitis treated at the Gastro-Intestinal Unit of the Western General Hospital, Edinburgh, in 17 consecutive years to July 1967, 55 patients, on certain criteria, were considered to have suffered from toxic dilation (table 1). Only patients who were severely ill and showed dilation on either clinical or radiological examination were included. All subjects had radiological evidence of dilation, but only 24 showed the clinical features of either abdominal distension or rebound tenderness, or both. In the analysis of the records a patient was considered to be "toxic," i.e., severely ill, if he or she showed any three of the four criteria in group A together with any one of the four in group B. Taken into account also was the clinician's impression of severity recorded at the time of the attack in which the complication occurred. The majority of the cases fulfilled all of the criteria in both groups. Material for histological confirmation and diagnosis was available from operative or necropsy specimens in 46 of the 55 patients. Although there were many acutely ill patients in our total experience of ulcerative colitis, these cases were not included in this survey unless they met the criteria already men-

2. Composition of series by sex and age at onset of disease

Age at onset

Female

Male

;yrs

Q-9 1Q-19 20-29 3Q-39 4Q-49 5Q-59 6Q-69 7G-79 SG-89

4

3 3 7 4 0 0

1

1 32

23

Totals

TABLE

0 2 10 6 5 2 5

0 2

3. Duration of disease at time of development of toxic dilation First attacks

Relapses

Months

No. of patients

Years

No. of patients

Q-3 4-6

20 3

%-5 6-10

22 6

10+

4 32

Total

23

JALAN ET AL.

70 TABLE

4. Extent of

disease~

Entire .... .. . . ..... . .. . . . .... . . Partial. .. . . . . ..... . .... . . . . ... . Segmental ... .... . .... .. .... . . .

43 7 2

Total .. .......... ....... ... ... .

52

~ Mode of determination: by examination of resected specimen (46); by radiology (6); and not determined (3) .

tioned. The evaluation of the management and prognosis of those patients without distension of the colon will be reported separately. The selection of patients was based solely on the criteria stated and not upon therapy or its outcome. Included in the series are patients treated before the introduction of corticosteroids in the management of ulcerative colitis. Composition of patient group. The group comprised 23 males and 32 females (table 2). Thirty-two per cent were less than 30 years old, 47% were between 30 and 59 years old, and 20% were over age 60. Males and females were equally distributed in the three age groups. First attack or relapse. Twenty-three patients developed this complication during the first attack c,>f colitis and 32 during a relapse. A patient was arbitrarily included in the relapse group if he or she had had continuous symptoms for 6 months or more. Duration of disease. In the group of patients who developed toxic dilation in the first attack the complication appeared within 3 months of the onset of symptoms (table 3). In the relapse group, although there was a wide variation in the length of history, the majority had had colitis for less than 5 years. Extent of involvement of colon. In all but 2 of the patients who died or underwent operation, the extent of involvement was determined by examination of the resected specimen. Of the total of 55 patients, there were 3 subjects in whom, while there was no doubt that their condition satisfied the criteria for the diagnosis of toxic dilation, the extent of the disease could not be subsequently determined. One subject recovered without surgery and, by the time barium studies were considered safe, the radiological appearances suggested that considerable recovery must have occurred. Another died after the formation of a temporary ileostomy and autopsy was refused . The third subject came to opera-

Vol . 57, No . 1

tion before a barium enema could be safely performed and the resected colon was inadvertently discarded by a department of pathology. The majority had disease affecting the whole colon. In 7 patients with partial involvement, the disease was limited to the right side of the colon in 1 and to the left side in the remaining 6. In 2 patients only the transverse colon was found to be involved. Five patients in whom the rectum was not affected included 1 with right-sided colitis, 2 with segmental colitis, and 2 with total involvement of the colon (table 4).

Results Precipitating Factors The cause of colonic dilation during an acute attack of ulcerative colitis remains obscure. Suspected agents have included opiates/ 5 - 17 anticholinergics, 15 and corticosteroids. 12 We have retrospectively examined the possible influence of these drugs and also of hypokalemia, 6 of distal stenosis, and of pregnancy. Twelve patients received opiate preparations in the form of Tincture opii or codeine phosphate within 48 hr of the deterioration in their general condition. One patient who died had had a ganglion-blocking agent; i.e., hexamethonium bromide. Three patients developed dilation during pregnancy and 2 in the immediate postpartum period. Seven patients had a barium enema performed within 1 week prior to the development of marked colonic distension and, in 2, perforation occurred within 24 hr of this examination. In only 3 patients 5. Outcome of medical management in relation to general conditions of the patient on admission (excluding those treated by immediate surgery)

TABLE

Outcome~

Seriously ill . ... Moderately ill .. .. ...

..

Totals ... . . . . . . . . . . . . .

Death

Recovery

17 4

10 14

21

24

• 0.025 > P(X 2 = 5.658) > 0.010; df (degrees of freedom) = +1.

TABLE

6. Effect of age at onset of symptoms and sex on the outcome Outcome Malea

Total

Age

,,s

Femaleb

Death

Recov- Death Recovery ery

--

-- -- --

Recovery

Death

-- --

G-29 3G-59 60 and over

9 11 5

9 15 6

2 5 0

4 8 4

7 6 5

5 7 2

Totals

25

30

7

16

18

14

= 0.254, not significant; df = +2.

a

X2

b

0.20

>

71

AN EXPERIENCE OF ULCERATIVE COLITIS

July 1969

P(X 2

= 2.631) >

0.10; df

=

+2.

was there histological evidence of stricture in the pelvic colon. Thirty per cent of the cases had a serum potassium of 3.0 mEq per liter or less on admission. A temporal relationship between the use of corticosteroids and the development of colonic distension was not found . Outcome The overall mortality of the present series was 45.5 ~(; . A preliminary inspection of the data for objective criteria which would allow the separation of patients with toxic dilation into moderately ill and severely ill categories proved unsuccessful. A significant difference in the outcome, however, was demonstrated when this separation was based on the clinician's initially recorded impression of severity (table 5). The immediate outcome of patients with this complication was examined in relation to a number of factors including sex, age, extent of involvement of bowel by the disease, rapidity of onset, and the presence or otherwise of metabolic disturbance. It was realised that, because of the small numbers involved, statistical proof of the influence of some of the factors on the outcome might not be obtainable. Nevertheless, because of the high mortality and of differing responses of patients to the same mode of treatment, it

was considered worthwhile to analyze the data in the hope of revealing features which might guide prognosis. Influence of sex and age. A clearly significant difference does not emerge, but nevertheless the figures suggest that females may have a poorer prognosis (table 6). Analysis of the data did not support the possibility that this might be related to the extent of involvement or the severity of the disease. Age does not seem to have any influence on the short term outcome. In relation to the first attack or relapse. Edwards and Truelove 18 and more recently Watts et al. 1 ~ have suggested that first attacks are more dangerous than relapses. In this present series no significant difference is shown in the mortality of subjects developing toxic dilation during a first attack or during a relapse (table 7). Relation to mode of onset. Information was available in the case records about the mode of onset and accordingly the patients have been divided into two groups, those of sudden onset and those with gradual onset. A sudden onset is defined as one in which symptoms reached maximum severity within 1 month of commencement. A gradual onset is one in which the maximum severity of symptoms was not reached until 1 month after the appearance of symptoms and signs. The possibility that the suddenness of onset influences prognosis is not borne out by statistical analysis (table 8). Relation to the extent of disease. This 7. Relationship between outcome and whether patient developed the complication during a first attack or relapse

TABLE

Outcomea No. of patients Recovery

Death

First attack .... Relapse . . .... .. .

23 32

10 20

13 12

Total .... .. . ...

55

30

25

a

X2

= 1.261, not significant; df = + 1.

JALAN ET AL.

72 TABLE

8. R elationship between mode of onset of present attack and outcome Outcome• No. of patients Recovery

Death

Sudden .... . ... Gradual. .. .. .. ..

29 26

13 17

16 9

Total . . .. . .... ..

55

30

25

• X2 = 1.581, not significant; df = +1.

Vol. 57, No. I

come between patients with low and those with normal levels of potassium. Likewise, hypoalbuminemia (serum albumin less than 3 g per 100 ml) which was present in 80% of the patients, did not seem to influence the final outcome (table 12). Influence of medical treatment . In 45 patients the results are examined of a period of medical treatment before surgery or death. Ten patients who had surgical treatment early in the attack are not included as they have been considered separately. The outcome of the current attack was classified as follows: 1. Remission: A patient in this category regained normal health on medical treatment alone and never came to operation. All patients in this group achieved both clinical and sigmoidoscopic remission . 2. Improvement followed by elective surgery: The patients did not regain normal health but improved sufficiently to have elective surgery carried out during the same admission . 3. Deterioration and urgent surgery: The patients in this group deteriorated on medical treatment before or after admission to this unit. Surgery was carried out in the circumstances of deterioration and these patients have been classified as having "urgent surgery. " 4. Death: In this group a further subdivision is made into those in whom death occurred after medical treatment only, and those in whom death occurred subsequent to the provision of both medical and surgical treatment.

has been examined in 52 patients. Three patients have been excluded for reasons mentioned earlier. For the sake of simplicity, partial and segmental involvement have been considered together. It is notable that more than 50% of the patients with only partial involvement died , suggesting that this does not preclude a grave prognosis. Of the 9 who had partial involvement, 7 were females, of whom 4 died (table 9). Relation to duration of attack. In order to assess the relationship between the immediate outcome and the duration of the current attack prior to their referral, the patients have been arbitrarily divided into two groups: those in whom the attack was of less than 2 months' duration before referral and those in whom it was longer. When dilation appears within 2 months of the onset, the prognosis appears worse (table 10), although the numbers do not allow statistical proof. Relation to the total duration of dis ease. We have found it of value to divide cases of colitis into those of short and of long TABLE 9. R elationshi p of extent of disease and outduration, according to history, by a divicome• sion at 3 years. The data suggest that those in whom the complication appears within Outcome No. of Extent 3 years of onset of colitis have a poorer patients Recovery Death prognosis (table 11), despite the lack of -- -statistical proof. Entire ....... . . . .... .. .... 43 24 19 Relation to values of serum potassium Partial and segmental. ... 9 4 5 and albumin at the time of admission. A serum potassium level of less than 3.0 Total .. ... . . . . .. ...... . . .. 52 28 24 mEq per liter was present in 30% of the patients on admission. There was no sig• Not determined in 3 patients, 1 died and 2 nificant difference in the short term out- recovered.

TABLE

10. Outcome in relation to duration of present attack

Duration of attack

Outcome•

No. of patients

Recovery

Death

42 13

20 10

22 3

55

30

25

mos

<2 >2 Total

73

AN EXPERIENCE OF ULCERATIVE COLITIS

July 1969

• 0.20 > P(X 2 = 2.356) > 0.10.

Since these cases were collected over a period of 17 years, the management has altered with therapeutic advances and, in particular, with the introduction of corticosteroids in 1955 and 1956. Recently, for reasons which will become obvious, our policy in the management of this complication has been altered to a short initial period of resuscitation followed by elective surgery. The management regimes are divided as follows : 1. Ten patients received supportive therapy only in the form of antibiotics, blood transfusion, and adequate replacement of fluid and electrolytes, but did not receive corticosteroids. Seven of these patients were managed prior to 1955. 2. Thirty-five patients received corticosteroid therapy. This unit has been concerned with ensuring adequate dosage of corticosteroids or corticotrophin in the management of severe ulcerative colitis and most patients so treated received up to 120 units of corticotrophin or the equivalent of 300 mg or more of hydrocortisone daily. Particular attention was given to the replacement of protein losses, initially by intravenous infusion and later orally. All patients received full supportive therapy. When optimal improvement was achieved by these means, these patients were offered elective surgery. 3. Ten patients had early surgery; i.e., after a minimal period of medical management lasting on an average of 4 days (range, 1 to 9 days).

Results of management regimes. Of the 10 patients who received supportive therapy, only 1 achieved complete remission and there were 6 early deaths (table 13). The majority of these patients were seen before the introduction of corticosteroids and intensive care therapy or were admitted in a severely ill state, having failed to respond to treatment in other hospitals. The results in this group should be compared with those in the second one of 35 patients who had corticosteriods in addition to supportive therapy in which 6 obtained a remission and 4 died. The object of this particular therapeutic regime, as has been mentioned, was to enable the patients to achieve optimal improvement prior to elective surgery. In the group treated by supportive measures only, this object was never achieved, whereas in the group which had corticosteroids in addition, 17 patients improved and had subsequent elective surgery. In this group of 17 patients, there was only one death which was due to air embolism during intravenous infusion. When deterioration occurred despite medical treatment, urgent surgical intervention became necessary. In the group of 10 patients receiving supportive treatment only, 3 showed this deterioration, all of whom died following surgery. The results in the corticosteroid-treated group were little better, with 8 of the 35 patients deteriorating and 7 dying. In the third group of 10 patients who had "early" surgery there were ultimately 4 deaths, 1 of which occurred TABLE

11. Relationship of the total duration of the diseas e at referral to the outcome

Total duration of disease

Outcome• No. of patients Recovery

Death

20

16 14

19 6

55

30

25

yrs

<3 >3 Total

35

• 0.20 > P(X2 = 2.127) > 0.10; df =

+1.

74

Vol. 57, No. 1

JALAN ET AL.

fied according to the timing of surgery (table 15) . One-stage proctocolectomy and ileostomy was performed in 18 patients and total colectomy and ileostomy in 10. Primary colectomy and ileorectal anastomosis was carried out in only 2 patients. Of these, one did not have any rectal involvement and in the other patient this was carried out as the patient refused an ileostomy. Six patients had only a limited procedure such as an ileostomy because their poor state appeared to contraindicate extensive surgery. Of the 6 patients who had a limited procedure, 2 were managed before the introduction of corticosteroids, and 4 subsequently. The figures suggest that, as an elective procedure, one-stage proctocolectomy is the operation of choice, but total colectomy with ileostomy is a satisfactory alternative for emergency situations. We have no evidence to support the use of a lesser procedure, such as ileostomy alone, in the operative treatment of a patient with toxic dilation.

12. Outcome related to the serum albumin and serum potassium level at the time of admission

TABLE

Outcome Death

Recovery

20 5

20 10

.. ..

25

30

Potassium levelb Hypokalemia ... . .. . . .. .. Normal potassium . . . . ...

8

7

17

23

25

30

Albumin level" Hypoalbuminemia ... .. . Normal albumin . .. . . .. . . Total .. .. .... . . . . . ...

Total. . . . . . . . . . . . .

"X 2 = 0.642 df = + 1, not significant . b x2 = 0.172 df = +1 , not significant.

shortly after operation due to bacteremia and acute renal failure. The 3 other deaths did not occur until after 5, 6, and 24 months, respectively. The patient who died after 5 months had had an initial ileostomy followed 5 months later by partial colectomy and died in the immediate postoperative period after this second procedure. The patient who died at 24 months had a staged colectomy and died after a third operation with postoperative bacteremia. The other patient, as also those who recovered, had total colectomy followed later by excision of rectum, but died 1 week after the second procedure (table 14).

Important Clinical Associations Important complications associated with toxic dilation which contributed to a deterioration in the general condition have been considered (table 16). Some patients had more than one complication. Perforation. This complication was associated with a very high mortality. In our experience it is exceedingly rare for perforation to occur in the absence of toxic dilation. Perforation occurred in 16 patients, of whom 12 died. Contrary to the experience

Type of Operation Thirty-eight patients were operated upon. The operations have been classiT AB LE

No. of

13. Results of m edical management Medical treatment only

Medical treatment and subsequent surgery

patients

---

Supportive. . . . . . .. Adrenocort icotropin and/ or steroids .

Remission

Death

---

---

10

1

6

35

6

4

Improvement and e lec tive surgery

Deterioration and urgen t surger y

Total mortality

- --

17 (1 death)

3 (3 deaths)

9

8 (7 deaths)

12

75

AN EXPERIENCE OF ULCERATIVE COLITIS

July 1969

In severely ill patients the detection of perforation may be difficult. Plain X-rays Outcome may reveal none of the diagnostic features No. of patients of perforation because of sealing off of the Recovery Death affected area. Massive hemorrhage. This is defined as 10 4• 6 a sudden or continuous heavy bleeding • Only 1 early death, 3 late deaths at 5 months, requiring immediate transfusion. It oc6 months, and 24 months, respectively . curred in 6 patients. It is of interest to note that in three instances massive hemof other authors, perforation occurred in orrhage accompanied the onset of toxic 11 patients during a relapse of the disease dilation. One of these patients also had and in only 5 during the first attack. Of perforation of the colon. Three of the 6 the 16 who had perforation, 11 were fe- patients died. males and 5 males. Clinical observation Bacteremia. In 38 patients blood culprovided a diagnosis of perforation in only tures were obtained on admission. In 11 7 of the subjects. In the other 9 it was the cultures were positive, 9 had gramdetected only at operation or at autopsy. negative bacteremia and in 2 StaphyloPerforations were often multiple (5 cases). coccus aureus was grown. Nine of the 11 Perforation, when single, occurred most patients with bacteremia died. In less frequently in the transverse or pelvic than half of these perforation had occolon. curred. Four patients in this group died before As has been demonstrated there is no TABLE

14. Results of immediate surgery

15. Type of operation in relation to timing of operation

TABLE

Proct ocolectomy (one-stage) .. Staged proctocolectomy . .. . . ... . . . Total colectomy .. . . . . . . . . . . . . . . . . Ileorectal anastomosis . . .. . . . . . .. Ileostomy alone . . . . . . . . . . . . . ' .. . . Transverse colostomy. . . . . . .... .. . Laparotomy .. •

Total. ...

















.. ....





.





0











0

.. . . . .. . .

No. of patients

Elective surgery

18

15 (14") 0 1 (1 a) 1 (I• ) 0 0 0

2

10 2 2 2 2

38

17

Urgent surgery

Immediate surgery

2 (1•)

1

0

2

2

7 (6•) 0 0 0 0

1 2 2 2

11

10

• Patients recovered.

any surgical procedure could be performed and, of the 12 who had surgical treatment, only 4 survived. Of the 7 patients in whom a preoperative diagnosis of perforation was made, the interval between diagnosis and operation was 2, 3, 4, 6, 9, 90, and 120 days, respectively. In the latter 2 patients the perforation was managed conservatively. They later underwent one-stage proctocolectomy and survived. Analysis of the data does not suggest that the use of corticosteroids increased the risk of perforation.

16. Incidence of associated clinical, biochemical , and radiological featur es

TABLE

Perforation . . . Massive hemorrhage . Bacteremia• . Distal stenosis . . Hypoalbuminemia (on admission) Hypokalemia (on admission) .. . ..

•••••••••

•••••••

0

0

••

••

0





No. of patients

%

16 6

29 10

11

3

28 5

40

80

15

30

• Blood culture obtained in only 38 patients.

76

JALAN ET AL.

Vol . 57, No. 1

30 significant difference in the overall mortality between the group which had medical treatment prior to surgery and the 20 group which had early surgery. The question therefore arises as to which is the No' of best form of management once the diag- Deaths nosis of toxic dilation is established. To answer this the data were analyzed in the following ways.

........................................................................................

"/

so •o ro •o no Time Interval Between Diagnosis of Days Toxic Dilation and Death FIG . 2. Cumulative number of deaths after the The proportion of deaths is expressed onset of toxic dilation . as percentages, which occurred at different time intervals following the di- deaths are included, there remains no agnosis of toxic dilation (fig. 1). A com- significant difference in the mortality rate parison is made between the patterns between the two groups. It is therefore observed in those patients who had early reasonable to conclude that a policy of surgery and those treated medically with early surgery for toxic dilation will proa view to elective surgery. It can be seen duce a marked fall in the early mortality that the majority of deaths in the ~edi­ and probably also a considerable fall in cally treated group occurred within 30 overall mortality. days of onset, most of these within the first 10 days. On the other hand, most of Cumulative Number of Deaths after the deaths in the small group of patients Onset of Toxic Dilation treated by early surgery occurred after Calculation of the data in 45 patients 120 days. Even when these three late who had prior medical management indicates that the likelihood of survival falls in the first 10 days of toxic dilation, although in view of the small numbers it cannot be proved statistically (fig. 2). This experience suggests that, if surgical intervention is to produce best results, it must be undertaken within this period. 10

20

JO

40

10

100

110

MOIITALITY Of [A,IILY SUIIGUtY

~ltC~TACt

TOTAL

lroiOitfALifY

<60

..

r--

MOIITilLITY Of I.I£ 01C AL TII(A TM[Nf WITN 0 1 WITHOIJT LAT[II SUIIG[If't' -

..

'ti'CtNTAGt fOTAL WC)ttft.LITY

4 7 '"' < UI •t

.-s <•u•

[6n I"'TU!V4L fii()M DIAGNOSIS TO D[ATH IN 04YS

FIG . 1. Interval from diagnosis of toxic dilation to death shown separately for 45 patients treated medically and 10 patients on whom early surgery was performed.

Time Interval between Diagnosis of Toxic Dilation and Improvement or Deterioration The main argument against early total colectomy is that, as described above, 70% of the patients will improve during a prolonged period of intensive medical management. Further analysis of the data (fig. 3) is based on the progress of the patient following the diagnosis of toxic dilation using the same time interval as shown in figure 1. The group here is divided into two categories, i.e., those who improved and those who deteriorated or died on the regime of prior medical management.

77

AN EXPERIENCE OF ULCERATIVE CO LITIS

July 1969

DUEJtiORAT[O GROU P IMP'tt0V(0 GROUP

P[ltC[NTAG[

OP CIIOUP

_,,._

I'CACO.ITAG£

OP GOOUP

lllll t: RVAL FAOII.I

OIAGN 0$1 $ TO

OEfEA IO AA TIO N O A IMP" 0V[MENT, IN OAV$

FIG. 3. Interval from diagnosis of toxic dilation to deterioration or improvement in 45 patients treated medically. Graph above derived from the histogram shows the approx imate cross-over point at 11 days.

Most of the patients deteriorated or died within the first 10 days, whereas improvement is apparent only after this period. A graph derived from these data in figure 3 shows the cross-over point at approximately 11 days. Current Status of Survivors of Medical Regime Seven patients obtained clinical and sigmoidoscopic remission on medical treatment. Although it was our policy to advise all patients with this complication to have surgery, it was not applied for a variety of reasons in seven instances (table 17). Most of these patients have remained well with minor exacerbations on followup which has varied from 1 to 10 years. These are the only patients who can be considered as having achieved remission with conservative treatment of toxic dilation. In 1 patient the colon, even though badly damaged, returned to normal. Persistence of inflammatory activity was noted on repeated rectal biopsies in all of the other subjects despite clinical remission and normal sigmoidoscopic ap-

pearances. Radiological abnormality likewise persisted on the barium enema studies in these 6 subjects. T ABLE

17. Status of medical s1trvivors on discharge and follow u p

Patient"

Follow-up

P. F.

None

J . R.

Minor relapses

A. F.

No symptoms

J. D. N. K.

Minor exacerbat ions None

D . I.

Minor relapses

J. M.

Died s uddenly: myo cardial infarct (?)

a

Reason for not operating

Social and religious objection from patient Pat ient declined surgery P atient declined surgery P atient declined surgery Good initial response m the first attack Good initial response In t he first attack Initial diagnos is in doubt

Status on discharge, remission.

78

JALAN ET AL.

Discussion The. present study has shown that the management of the complication of "toxic dilation" remains a serious challenge to both physician and surgeon. Our experience emphasizes the importance of recognizing, at an early stage, that a patient has developed this complication the criteria for which has been suggested. ' Although a large volume of literature has accumulated on the clinical and pathological aspects of "toxic dilation" and "ac\_\te fulminating" ulcerative colitis there is still no agreement on a definitio~ of 'either of these entities. It is possible that I what has been described as acute fulminating ulcerative colitis may be a predilation stage. Brooke20 has said that a fulminating episode "beggars exact definiti(;m" and suggested as criteria "severe ~oxemia, pyrexia to 103 F, lethargy vergmg on coma and serious alteration of blood chemistry." Since precise definition seems impossible, it is suggested that the term fulminating should be discarded and that severe attacks should be divided into tho~e with or without colonic distension. "Toxic dilation" may be a misleading ter,m in that it implies a causative mechanism for dilation which is unproved. Nevertheless the term indicates the two essential features of this complication. Toxicity is difficult to define. Attempts to recognize the objective criteria continue, but presently in borderline cases we have found it necessary to rely upon the clinician',s recorded impression of severity of illness. The clinical features which appear to indicate a severe attack are pyrexia above 100 F, an erythrocyte sedimentation rate above 30 mm per hr, leucocytosis, tachycardia, and hemoglobin level below 60% (yY. I. Card, personal communication). J:?ehydration, mental changes, hypotensiOn, and electrolyte disturbance appear late and are not mandatory for the diagnosis of a severe attack. Diagnosis In the definitive diagnosis of dilation plain films of the abdomen are crucial:

Vol . 57, No. I

This is especially so as marked radiological distension of the colon may occur without clinically obvious abdominal distension. In episodes of severely active ulcerative colitis they should be repeated if failure to induce improvement raises suspicion of the development of the complica~ion . In the majority of patients, for physical reasons, the transverse colon is the part most prominently distended. Haustral formation is absent in the involved segment. Most films will also show numerous broad based nodular projections of surviving epithelium extending into the gas-filled lumen of the bowel (" pseudopolypi "). The caliber of the distended colon may vary, and while anything above 7 em should be considered abnormal, it cannot be overstressed that any degree of distension developing in a toxic patient is ominous and demands immediate attention (figs. 4 to 6). The characteristic histopathology of this complication is transmural extension of the disease over a wide area. This was confirmed in all of the patients in whom an examination of the resected specimen was made. Destruction of ganglion cells as suggested by Bockus et al. ~ was not a marked feature in our pathological studies. Transmural extension without dilation is very uncommon even in the severely ill patient. Etiology The factors which unleash the transmural extension of an essentially mucosal disease remain unknown. Cohn and his associates 6 implicated hypopotassemia as a cause of colonic distension. In the present study only 30% of the patients had a serum potassium level below 3.1 mEq per liter on admission. Hypokalemia is more likely to be an indication of the severity of the illness rather than a primary cause of dilation, but at a certain stage in the development of the complication may contribute to loss of tone in the muscle wall of the colon . Smith et al. 15 were the first to show a temporal relationship between the use of

July 1969

AN EXPERIENCE OF ULCERATIVE COLITIS

79

FIG . 4 (left) . Plain film of abdomen from a patient suffering from ulcerative colitis showing slight distension of descending colon, loss of haustration, and fecal collection in the ascending and transverse colon. FIG . 5 (middle). Same patient 5 days later, showing distension of transverse colon. FIG . 6 (right) . Same patient 18 days later, showing dilation of transverse colon, loss of haustration, and irregular mucosal outline.

anticholinergic drugs, opiates, and barium enema and the onset of toxic dilation. Recently Garrett et al. 16 reviewed 36 cases of toxic dilation seen at the Mayo Clinic and found that, in 17, opiate therapy was initiated or increased in dosage shortly before clinical recognition of colonic distension. These authors also carried out colonic motility studies, after administration of 15 minims of Tincture opii, in 14 patients with mild to moderately severe ulcerative colitis and found that even in this small dosage the drug was a potent stimulant of colonic motility. On the basis of this experimental work they have suggested that the "hypermotility and increased tonus changes produced by narcotics in patients with chronic ulcerative colitis may bear a relationship to the development of 'toxic dilation' of the colon when these drugs are administered to patients with acute fulminating form of the disease." They suggest that this increased tonus and hypermotility may either be permissive to the penetration of the muscle by the necrotizing inflammatory reaction associated with a severe attack of colitis or that localized pressure from segmenting contraction of circular muscle fibers may overcome the remaining tone of the muscle allowing dilation. In the present study there was a sugges-

tion that in 12 patients opiate preparations could have been associated with colonic distention but we have been unable to show a consistent temporal relationship between the use of drugs and the onset of dilation. Opiate preparations have been used very widely for symptomatic treatment of diarrhea but in view of the study of Garrett et al. it see111s wiser to avoid the use of these drugs in severely ill patients. None of our patieqts received anticholinergic agents and consequently no relationship between this mode of treatment and toxic dilation occurs in this series. Smith et al. 15 and recently Odyniec et al. 21 have related the onset of colonic distension to administration of barium enema. In most of our cases barium enema was delayed until overall improvement had occurred. In our series, in only 5 cases did the colitis appear to worsen subsequent to a barium enema. Two patients had a barium enema performed 2 days before perforation occurred. Much more difficult to assess is the role of pregnancy in the precipitation of an attack of toxic dilation. de Dombal et al. 22 in their retrospective analysis of 107 pregnancies occurring in 72 patients found no evidence of an adverse effect on ulcerative colitis, but they did comment

80

JALAN ET AL.

on the frequency of severe attacks during the first trimester and the puerperium. This relationship is currently being studied in our own series and will be reported later.

Vol. 57, N o. 1

Management The present study has shown that patients with this particular complication of ulcerative colitis suffered appreciable mortality despite admission to a unit where a group of physicians and surgeons Outcome are particularly interested in the disease Toxic dilation complicated 13% of the and have the management of each case in 399 patients with colitis attending our joint care. It is difficult to compare our unit. This is a much higher incidence results with others because published than has been reported by others. Ed- series are small and definitions of toxic wards and Truelove 18 reported an inci- dilation, modes of management, and esdence of 1.6% in 624 patients reviewed pecially the criteria and circumstances by them. Mclnerrey et al. 10 reported an of operation vary. The difference in morincidence of 2.9% in 1230 patients seen at tality in relation to timing of surgery is the Mayo Clinic. quite obvious from our study. This, to The higher incidence in our series prob- some extent, explains the discrepancy in ably reflects the selective nature of the the mortality rate reported by other aucolitis population studied and does not thors and which varies from 10%23 to represent the spectrum of disease in the 50%.8 Our high mortality rate of 45.5% general population. A large proportion of reflects the inclusion in the series of paour cases were referred from other hospi- tients treated in the precorticosteroid era tals where treatment had been com- and the concentration in the unit of semenced and often because that treatment verely ill patients referred from other appeared to be unsuccessful. hospitals. Overall, the short term morThe outcome has been analyzed in re- tality has shown a considerable improvelation to certain defined features. None ment in the postcorticosteroid era. Helpof these can be shown to be clearly sig- ful factors have been earlier referral from nificant except possibly that the prog- other units; increasingly early recognition nosis is less favorable in young females, of this complication; better understanding in those with a shorter total history, and of protein, electrolyte, and fluid needs; in attacks of short duration. The impor- and the introduction of corticosteroids. tance of the other factors cannot be as- The loss of protein in severe active ulsessed as the numbers were not large cerative colitis must be emphasized and enough to test the significance. We tried can reach 50 g per day. 24 The use of corto relate the outcome to certain features ticosteroids in toxic dilation is still a in the hope of identifying those which subject of controversy. We have shown put the patients at risk. From the data that supportive therapy without cortiexamined it has not proved possible to costeroids carries a very high mortality define these but the evidence suggests and would recommend that all patients that the group of patients in most danger receive corticosteroids whether or not of developing toxic dilation are females early surgery is being contemplated. In in the third or fourth decade with a short this series, although the results were history, a severe attack of recent onset, better in those treated with corticosand with extensive involvement of the colon. It also appears that the outcome is teroids, it should be noted that the fall in a product of the severity of the attack, mortality cannot be unreservedly asthe existence of dilation, and the presence cribed to the corticosteroids alone, as the or otherwise of complicating features, es- need for adequate replacement of protein pecially perforation, hemorrhage, and loss and for intensive care in general was bacteremia. also realized at the same time as the in-

July 1969

AN EXPERIENCE OF ULCERATIVE COLITIS

81

troduction of cortisone and corticotrophin come to operation. Delay carries the risk in the management of the disease. of enforced operation upon a deteriorating Our earlier experience taught us the patient, with its attendent grave prognecessity for an intensive approach to nosis. Surgery may be technically easier in management requiring unceasing atten- the earlier stages of acute dilation, espetion by nursing and clinical staff, con- cially if perforation has been forestalled. stantly monitoring progress and utilizing Once the decision for surgery has been every means available to bring the dis- made, the operation of choice seems to be ease under control. These include, in ad- total colectomy and ileostomy. In the madition to corticosteroids or corticotrophin, jority of cases subsequent excision of the antibiotics; constant replacement of wa- rectum will be required. ter, electrolyte, mineral, and protein REFERENCES losses; and provision of adequate calories 1. Case Records of Massachusetts General Hospi· and vitamins. In an attempt to reduce the tal. 1933. Case 19023, Surgical Department incidence of bacteremia in such ill cases, presenting case. New Eng. J. Med. 208: 94- 95. we have adopted the practice of routinely 2. Case Records of Massachusetts General Hospiusing broad spectrum antibiotics after tal. 1937. Case 23201, presentation of a case. blood has been withdrawn for microbiNew Eng. J. Med . 216: 894- 896. ological study. Occasionally, feeding gas- 3. Case Records of Massachusetts General Hospitrostomies in the totally anorexic makes tal. 1941. Case 27242, presentation .of a case. it possible to avoid the overuse of the New Eng . J . Med . 224: 1029- 1031. parenteral route. It is appreciated, there4. Jobb, E., and A. Finkelstein. 1947. Interesting X-ray findings in a case of acute fulminating fore, that the severe type of case at risk ulcerative colitis. Gastroenterology 8: 213for the complication of dilation should 220. be managed in an intensive care area . If, 5. Chisholm, T. C. 1946. Acute fulminating ulon medical management alone, improvecerative colitis with massive perforation and ment occurs, the prognosis is good, otherperitonitis: report of a case. Arch. Surg. (Chiwise the outlook is poor, despite the subcago) 53: 462- 476. sequent use of surgery. If the patient 6. Cohn, E. M., P. Copit, and H. J . Tumen . 1956. responds to medical treatment and there Ulcerative colitis with hypopotassemia. Gasis no major fluctuation in the clinical troenterology 30: 950-957. 7. Madison, M. S., and J. A. Bargen. 1951. Fulstate, the prognosis appears equally good minating ulcerative colitis with unusual segwhether or not elective surgery is submental dilation of the colon : report of a sequently carried out. case. Mayo Clin . Proc. 26: 21- 24. Deterioration may be insidious and 8. Lumb, G., R. H. B. Protheroe, and G. S . difficult to assess in a patient already Ramsay. 1955. Ulcerative colitis with dilagravely ill so that many days may pass tion of the colon. Brit. J . Surg. 43: 182- 188. before recognition that a catastrophe has 9. Bockus, H. L., J . L. Roth, E. Buckman, M. occurred. Even though we have shown Kaiser, U. Staub, A. Finklestein, and A. that ultimate mortality does not differ Valdes-Dapena. 1956. Life history of nonbetween the group who had initial medispecific ulcerative colitis: relation of progcal treatment and the group who had nosis to anatomical and clinical varieties. Gastroenterologia 86: 549-581. early surgery, nevertheless, we would recommend early surgery once dilation 10. Mclnerrey, G. T., W. G. Sauer, A. H. Baggentoss, and J. R. Hodgson. 1962. Fulminating is recognized on the grounds that most of ulcerative colitis with marked colonic dilathe deaths in the medically treated pation : a clinico-pathologic study. Gastroentients occurred within 10 days, during terology 42: 244- 257. which period it is difficult to assess 11. Roth, J . L. A., A. Valdes-Dapena, G. N. Stein, progress. A further argument in favor of and H . L. Bockus. 1959. Toxic megacolon in early and elective surgery is that most ulcerative colitis. Gastroenterology 37: 239of the patients with dilation ultimately 255.

82

JALAN ET AL.

12. Marshak, R. H ., B. E. Korelitz, S. H. Klein, B. S. Wolf, and H. D. Janowitz. 1960. Toxic dilation of the colon in the course of ulcerative colitis. Gastroenterology 38: 165-180. 13. Peskin, G. W., and A. V. 0 . Davis. 1960. Acute fulminating ulcerative colitis with colonic distension. Surg. Gy nec. Obstet. 110: 269-276. 14. Lens, E. , J . De Groote, J . Vandenbrooke, and P. Wellens. 1962. Dilation aigue du colon, complication de Ia colite ulcero hemorragique . Acta Gastroent. Belg. 25: 783-793. 15. Smith, F. W., D. H. Law, W. F. Nickel, and M. H. Sleisenger. 1962. Gastroenterology 42: 233243. 16. Garrett, J . M. , W. G. Sauer, and C. G. Moertel. 1967. Colonic motility in ulcerative colitis after opiate administration. Gastroenterology 53: 93- 100. 17. Kirsner, J . B. 1962. Discussion. Gastroenterology 42: 256-257.

Vol. 57, No . I

18. Edwards, F. C., and S. C. Truelove . 1963. The course and prognosis of ulcerative colitis. Gut 4: 299-315. 19. Watts, J. M. , F . T . de Dombal, G. Watkinson, and J. C. Goligher. 1966. Early course of ulcerative colitis. Gut 7: 16-31. 20. Brooke, B. N. 1956. Outcome of surgery for ulcerative colitis. Lancet 2: 532-536. 21. Odyniec, N. A., E. S. Judd, and W. G. Sauer. 1967. Toxic megacolon. Arch. Surg. (Chicago) 94: 638- 643. 22. de Dombal, F. T ., J. M. Watts, G. Watkinson, and J. C. Goligher. 1965. Ulcerative colitis and pregnancy. Lancet 2: 599-602. 23 . Wolf, B. S. , and R. H. Marshak. 1959. "Toxic" segmental dilation of colon during course of fulminating ulcerative colitis. Amer. J. Roentgen. 82: 985- 995. 24. Falconer, C. W. A. 1960. Ulcerative colitis. J . Roy. Colt. Surg. Edinb . 5: 269-286.