Acta Med Scand Suppl. 603:43-46,
1977
Intensive treatment in severe acute attacks of ulcerative colitis H. Schjmsby, P. Heimann, D. Kremer, K. NordgBrd, T. S. Raugstad, F. Ringheim and 0. Stray Medical Dgartments A and B , Dekartment of Surgery, Haukeland Sykehus, University of Bergen, Norway
ABSTRACT. The results of intensive treatment including steroids and early surgery in severe colitis in the period 1971-1975 were compared to the results from the period 1966- 1970, when systematic intensive therapy was not given. The period of preoperative medical treatment was reduced on average from 31 to 17 days. Approximately half the patients went into remission in each period. I n the period 1971- 1975 (23 patients) there was no mortality during the acute attacks or in the subsequent follow-up period. I n the period 1966- 1970, the immediate mortality in 30 patients was 10% (3 patients). One patient died six years later at the age of 81 during a relapse of the colitis, and the overall mortality was 13.3%.
I n patients with severe attacks of ulcerative colitis there is a high fatality rate (2). Remissions can be encouraged by using corticosteroids (9) and possibly also by intensive intravenous therapy (10). Nevertheless the use of steroids in acute attacks is still being debated, as the overall mortality in patients on steroid treatment appears t o be high (6, 10). Early surgery in patients who faiI to improve on conservative treatment has also been proposed to reduce the fatality rate (4, 5). Early in 1971, a closer form for cooperation was carried out between the departments of Medicine, Surgery and Anaesthesiology in the treatment of severe ulcerative colitis. We adopted a policy of intensive intravenous therapy including steroids and early surgery in patients who failed to go into remission: We present here the results from a 5-year trial period.
PATIENTS AND METHODS During a 10-year period from 1. January 1966 to 31. December 1975 148 patients with ulcerative colitis were admitted to the hospital. 53 patients had acute severe colitis. 30 patients with severe attacks were admitted in the 5-year period before 31. December 1970, and 23 patients in the 5-year period from 1971. The age distribution is recorded in table I and the extent of involvement of the large bowel is shown in table 11. The diagnosis and the extent of the disease was established by sigmoidoscopy, barium enema, and in the operated patients by inspection and pathological examination of the resected specimens. The length of the history of the disease before the severe attack was nearly the same in the period from 1971-1975 (mean 1.6 years, range 2 weeks - 9 years) as in the period from 1966-1970 (mean 2 years, range 1 week - 8 years).
Table I. Age of patients with severe ulcerative colitis Age (years) 0-19 20-39 40-59 60 Mean age
1966-1970 (no) 11 10 5 4 33.0
1971-1975 (no) 6 9 . 6
2 32.1
Table 11. Extent of involvement of bowel 1966-1970 Extent (no) Distal (rectum and sigmoid) 0 Intermediate 10 Total 19 Unknown 1
971-1975 (no)
1 5 16 1
44.
H. Schjmsby, P. Heamann, D. Kremer, K . Nordgdrd, T.S. Raugstad, F. Rangheam and 0. Stray
The attacks of severe ulcerative colitis were classified according to the criteria of Truelove and Witts (9) which are: 1) Severe diarrhea (six or more motions a day) with macroscopic blood in stools. 2) Fever (mean evening temperature more than 37.5"C or a temperature of 37.8% or more on at least two days out of four). 3) Tachycardia (mean pulse rate more than 90 per minute). 4) Anaemia (haemoglobin 75% or less - allowance made for recent transfusion). 5) E. S. R. much raised (more than 30 mm in one hour). The mean values of the pulse rate, the number of stools per day and the temperature the two first days of the severe attack were calculated. In the period 1966- 1970 the mean number of stools was 8.9 (range 6-20), the pulse rate 105,9 (76- 140) and the temperature 38.3 (37.1-39.9). In the period 1971-1975 the mean number of stools was 10.5 (6-20), the pulse rate 102.8 (84- 127) and the temperature 38.1 (36.7 -39.2). Before 1st of January 1971 medical treatment of patients with severe ulcerative colitis included steroids, which were given to 19 of 30 patients. Total parenteral nutrition was not given. After 1st of January 1971 closer cooperation between the departments of Medicine, Surgery and Anaesthesiology was established. Patients with attacks of severe colitisweregiven total parenteral nutrition for five consecutive days. The intravenous regimen included proteins (2 g/kg bodyweigt/day) and total calories 30/kg bodyweight/ day. Corticosteroidswere given to all 23 patients except one in whom perforation was suspected. Prednisone was given orally until July 1974. After this time hydrocortisone 240 mg daily was given intravenously in four divided doses. Antibiotics were not included in the regimen. Conservativetreatment was continued in patients who went into remission or showed clinical improvement within the first 3-5 days. No improvement within the first few days or a deterioration in clinical condition was considered an indication for immediate colectomy. The mean duration of hospital medical treatment prior to surgery in the period 1971 -1975 ( 17 days, range 2 -36 days) was reduced compared to the period 1966- 1970 (31 days, range 0106 days).
Results The outcome of severe attacks of ulcerative colitis is shown in table 111. The proportion of patients who went into remission and were able to continue medical treatment was the same in the second (52%) as in the first period (50%).
Table 111. Short term results in patients with seuere ulcerative colitis
Result Remission (cont. med. treatment) Surgery Deaths lonlv after sureerv)
1966- 1970 1971- 1975 (no) (no) 15 15 3
12 11 0
Early mortality (table 111): I n the period 1966-1970 (30 patients, 33 severe attacks) three patients died after surgery, whereas none died during medical therapy. The early mortality in this period was lo%, whereas there was no early mortality in the period from 1971 -1975 (23 patients, 26 attacks). The operative procedures in the attacks of severe colitis are shown in table IV. The patient who died after colectomy and ileorectal anastomosis, a 42 year oId woman, was operated after a 6-week period of conservative treatment of her first severe attack. She died from peritonitis due to anastomosis leakage. The patient who died after colectomy and ileostomy and closure of the rectum was a 14-year old girl. She was submitted for immediate operation due to perforation of the colon. After the operation she was severely ill due to septicemia and died after 3 months. The patient who died after proctocolectomy, a 44-year old woman, was operated after 2 months hospital treatment of her Table IV. Operative procedures in severe attacks of colitis. Method
1966-1970 1971-1975 (no) (dead) (no) (dead)
Colectomy and ileorectal anastomosis 4 Colectomy, ileostomy and proximal closure of rectum 2 Colectomy, ileostomy and sigmoidostomy 4 Total proctocolectomy and ileostomy 5 Total 15
1
0
0
1
2
0
0
2
0
1 3
7 11
0
0
Treatment o f seuere ulceratzve colitas Table V. Long term results inpatients going into remission Mean length of follow-up :Period 1966- 1970, 8.4 years (range 4.7-11.0) ;period 1971-1975,3.9years (1.6-5.7) Result Remission Relapses medically treated Elective surgery Unknown
1966- 1970 1971- 1975 (no) (no) 6 2 5 7 3 3 1 0
first severe attack. She died one week after the operation due to peritonitis and septicemia. The long-term fate of patients followed up after going into remission on medical therapy is summarized in table V. I n the period 1966 -1970 one patient died during a relapse of the colitis six years after the severe attack at the age of 8 1. The overall mortality in patients admitted with severe colitis in the period 1966-1970 was thus 13.3%. Of the patients admitted in the period 1971-1975 none have died during the subsequent follow-up period.
Discussion The results show reduced mortality in the period 1971 -1975 compared to the period 1966 -1970. The change in overall mortality was mainly due to reduced operative mortality. In the first period the operative mortality in 15 patients was 20%) whereas none of 11 patients died after surgery in the second period. This fall in mortality was associated with a more intensive intravenous therapy and with a reduction in the time from onset of the attack until surgery. Each of these factors may have influenced the mortality results. There was, however, a limited number of patients and the difference in mortality could be due to chance. About half of the patients went into remission in each of the two periods. This is a similar proportion of success of medical treatment as reported elsewhere (5, 6, 10). In the second period, corticosteroids were given to a larger proportion than in the first
45
period, and total parenteral nutrition was given routinely only in the second period. Apparently this change in regimen did not result in alteration of the remission rate. Nevertheless one cannot exclude that the number of patients who went into remission was influenced by the tendency to operate earlier in the second period. Parenteral nutrition in severe ulcerative colitis can provide adequate nutrition (1) and be of value in preparing the patients for the trauma of colectomy (3). I t is, however, uncertain whether such treatment can induce a remission. In this material there was no change of the remission rate after introduction of parenteral nutrition. Improvement of the colitis on such treatment appears to be the exception rather than the rule (3, 4). Nevertheless Solassol et a1 (8) reported that remission was obtained and surgery avoided in 6 out of 12 patients receiving total intravenous nutrition without the addition of steroids. The value of using steroids in acute severe colitis is disputed. I t is possible that steroids may promote remission in severe colitis (6, 9, 10). Nevertheless the effect of corticosteroids on the fatality rate in severe attacks appeared to be less than in moderate attacks (2)) and in two recent publications (6, 10) steroid treatment in severe colitis was associated with an overall mortality above 10%. A controlled trial may be necessary to show whether steroids have a place in the treatment of severe colitis. Early surgical treatment of severe attacks has been associated with a reduced fatality rate (4,5), and the tendency to earlier surgery in the period 1971 -1975 in the present series may have contributed to the reduced mortality together with improved parenteral nutrition. Comparing two materials composed of individuals drained from the same area but at two different periods is inferior to a controlled trial, which would be the ideal way to encircle the optimal treatment of ulcera-
46
H. Schjmsby, P. Heimann, D. Kremer, K. Nordgird, T. S. Raugstad, F. Ringheim and 0. Stray
tive colitis. (7) Essential for comparability is the age of the patients, the extension of the disease, the length of the history prior to attack, and severity of the attack, since these parameters are known to influence the prognosis (2, 11). The two materiaIs show a different age distribution with a larger number of patients under 20 years in the first period (Table I), but the proportion of patients above 40 years was nearly the same in the periods, (mortality is known to increase in elder patients). The extent of the disease (Table 11) as well as the length of the history before the attack were similar in the two periods. Furthermore, important parameters of the disease activity had nearly the same value in the two periods.
4.
5.
6.
7.
8.
9. REFERENCES 1. Dudrick, S. J. & Ruberg, R. L.: Principles and practice of parenteral nutrition. Gastroenterology 61: 901, 1971. 2. Edwards, F. C. & Truelove, S. C. :The course and and prognosis of ulcerative colitis. Gut 4: 299, 1963. 3. Fischer, J. E., Foster, G. S., Abel, R. M., Abbot, W. M. & Ryan, J. A.: Hyperalimentation as
10.
11.
therapy for inflammatory bowel disease. Am J Surg 125: 165, 1973. Flatmark, A., Fretheim, B. & Gjone, E.: Early colectomy in severe ulcerative colitis. Scand J Gastroenterol 10: 427, 1975. Goligher, J. C., Hoffmann, D. C. & De Dombal, F. T.: Surgical treatment of severe attacks of ulcerative colitis, with special reference to the advantages of early operation. Br Med J 4: 703, 1970. Kristensen, M., Kondahl, G., Fischermann, K. & Jarnum, S.: High dose prednisone treatment in severe ulcerative colitis. Scand J Gastroenterol 9 : 177, 1974. Riis, P.: Therapeutic influence on the prognosis of ulcerative colitis. Scand J Gastroenterol 9: 1, 1974. Solassol, E., Joyeux, H., Pujol, H., Balmes, J-L., Cayrol, B. & Favier, C. : Hypernutrition parenttrale substitutive et rectocolites graves. Arch Fr Ma1 App Dig 63: 115, 1974. Truelove, S. C. & Witts, L. J.: Cortisone in ulcerative colitis. Final report on a therapeutic trial. Br Med J 2 : 1041, 1955. Truelove, S. C. & Jewell, D. P.: Intensive intravenous regimen for severe attacks of ulcerative colitis. Lancet 1: 1067, 1974. 1974. Watts, J. McK., De Dombal, F. T., Watkinson, G. & Goligher, J. C.: Early course of ulcerative colitis. Gut 7: 16, 1966.
1977
Intensive treatment in severe acute attacks of ulcerative colitis H. Schjmsby, P. Heimann, D. Kremer, K. NordgBrd, T. S. Raugstad, F. Ringheim and 0. Stray Medical Dgartments A and B , Dekartment of Surgery, Haukeland Sykehus, University of Bergen, Norway
ABSTRACT. The results of intensive treatment including steroids and early surgery in severe colitis in the period 1971-1975 were compared to the results from the period 1966- 1970, when systematic intensive therapy was not given. The period of preoperative medical treatment was reduced on average from 31 to 17 days. Approximately half the patients went into remission in each period. I n the period 1971- 1975 (23 patients) there was no mortality during the acute attacks or in the subsequent follow-up period. I n the period 1966- 1970, the immediate mortality in 30 patients was 10% (3 patients). One patient died six years later at the age of 81 during a relapse of the colitis, and the overall mortality was 13.3%.
I n patients with severe attacks of ulcerative colitis there is a high fatality rate (2). Remissions can be encouraged by using corticosteroids (9) and possibly also by intensive intravenous therapy (10). Nevertheless the use of steroids in acute attacks is still being debated, as the overall mortality in patients on steroid treatment appears t o be high (6, 10). Early surgery in patients who faiI to improve on conservative treatment has also been proposed to reduce the fatality rate (4, 5). Early in 1971, a closer form for cooperation was carried out between the departments of Medicine, Surgery and Anaesthesiology in the treatment of severe ulcerative colitis. We adopted a policy of intensive intravenous therapy including steroids and early surgery in patients who failed to go into remission: We present here the results from a 5-year trial period.
PATIENTS AND METHODS During a 10-year period from 1. January 1966 to 31. December 1975 148 patients with ulcerative colitis were admitted to the hospital. 53 patients had acute severe colitis. 30 patients with severe attacks were admitted in the 5-year period before 31. December 1970, and 23 patients in the 5-year period from 1971. The age distribution is recorded in table I and the extent of involvement of the large bowel is shown in table 11. The diagnosis and the extent of the disease was established by sigmoidoscopy, barium enema, and in the operated patients by inspection and pathological examination of the resected specimens. The length of the history of the disease before the severe attack was nearly the same in the period from 1971-1975 (mean 1.6 years, range 2 weeks - 9 years) as in the period from 1966-1970 (mean 2 years, range 1 week - 8 years).
Table I. Age of patients with severe ulcerative colitis Age (years) 0-19 20-39 40-59 60 Mean age
1966-1970 (no) 11 10 5 4 33.0
1971-1975 (no) 6 9 . 6
2 32.1
Table 11. Extent of involvement of bowel 1966-1970 Extent (no) Distal (rectum and sigmoid) 0 Intermediate 10 Total 19 Unknown 1
971-1975 (no)
1 5 16 1
44.
H. Schjmsby, P. Heamann, D. Kremer, K . Nordgdrd, T.S. Raugstad, F. Rangheam and 0. Stray
The attacks of severe ulcerative colitis were classified according to the criteria of Truelove and Witts (9) which are: 1) Severe diarrhea (six or more motions a day) with macroscopic blood in stools. 2) Fever (mean evening temperature more than 37.5"C or a temperature of 37.8% or more on at least two days out of four). 3) Tachycardia (mean pulse rate more than 90 per minute). 4) Anaemia (haemoglobin 75% or less - allowance made for recent transfusion). 5) E. S. R. much raised (more than 30 mm in one hour). The mean values of the pulse rate, the number of stools per day and the temperature the two first days of the severe attack were calculated. In the period 1966- 1970 the mean number of stools was 8.9 (range 6-20), the pulse rate 105,9 (76- 140) and the temperature 38.3 (37.1-39.9). In the period 1971-1975 the mean number of stools was 10.5 (6-20), the pulse rate 102.8 (84- 127) and the temperature 38.1 (36.7 -39.2). Before 1st of January 1971 medical treatment of patients with severe ulcerative colitis included steroids, which were given to 19 of 30 patients. Total parenteral nutrition was not given. After 1st of January 1971 closer cooperation between the departments of Medicine, Surgery and Anaesthesiology was established. Patients with attacks of severe colitisweregiven total parenteral nutrition for five consecutive days. The intravenous regimen included proteins (2 g/kg bodyweigt/day) and total calories 30/kg bodyweight/ day. Corticosteroidswere given to all 23 patients except one in whom perforation was suspected. Prednisone was given orally until July 1974. After this time hydrocortisone 240 mg daily was given intravenously in four divided doses. Antibiotics were not included in the regimen. Conservativetreatment was continued in patients who went into remission or showed clinical improvement within the first 3-5 days. No improvement within the first few days or a deterioration in clinical condition was considered an indication for immediate colectomy. The mean duration of hospital medical treatment prior to surgery in the period 1971 -1975 ( 17 days, range 2 -36 days) was reduced compared to the period 1966- 1970 (31 days, range 0106 days).
Results The outcome of severe attacks of ulcerative colitis is shown in table 111. The proportion of patients who went into remission and were able to continue medical treatment was the same in the second (52%) as in the first period (50%).
Table 111. Short term results in patients with seuere ulcerative colitis
Result Remission (cont. med. treatment) Surgery Deaths lonlv after sureerv)
1966- 1970 1971- 1975 (no) (no) 15 15 3
12 11 0
Early mortality (table 111): I n the period 1966-1970 (30 patients, 33 severe attacks) three patients died after surgery, whereas none died during medical therapy. The early mortality in this period was lo%, whereas there was no early mortality in the period from 1971 -1975 (23 patients, 26 attacks). The operative procedures in the attacks of severe colitis are shown in table IV. The patient who died after colectomy and ileorectal anastomosis, a 42 year oId woman, was operated after a 6-week period of conservative treatment of her first severe attack. She died from peritonitis due to anastomosis leakage. The patient who died after colectomy and ileostomy and closure of the rectum was a 14-year old girl. She was submitted for immediate operation due to perforation of the colon. After the operation she was severely ill due to septicemia and died after 3 months. The patient who died after proctocolectomy, a 44-year old woman, was operated after 2 months hospital treatment of her Table IV. Operative procedures in severe attacks of colitis. Method
1966-1970 1971-1975 (no) (dead) (no) (dead)
Colectomy and ileorectal anastomosis 4 Colectomy, ileostomy and proximal closure of rectum 2 Colectomy, ileostomy and sigmoidostomy 4 Total proctocolectomy and ileostomy 5 Total 15
1
0
0
1
2
0
0
2
0
1 3
7 11
0
0
Treatment o f seuere ulceratzve colitas Table V. Long term results inpatients going into remission Mean length of follow-up :Period 1966- 1970, 8.4 years (range 4.7-11.0) ;period 1971-1975,3.9years (1.6-5.7) Result Remission Relapses medically treated Elective surgery Unknown
1966- 1970 1971- 1975 (no) (no) 6 2 5 7 3 3 1 0
first severe attack. She died one week after the operation due to peritonitis and septicemia. The long-term fate of patients followed up after going into remission on medical therapy is summarized in table V. I n the period 1966 -1970 one patient died during a relapse of the colitis six years after the severe attack at the age of 8 1. The overall mortality in patients admitted with severe colitis in the period 1966-1970 was thus 13.3%. Of the patients admitted in the period 1971-1975 none have died during the subsequent follow-up period.
Discussion The results show reduced mortality in the period 1971 -1975 compared to the period 1966 -1970. The change in overall mortality was mainly due to reduced operative mortality. In the first period the operative mortality in 15 patients was 20%) whereas none of 11 patients died after surgery in the second period. This fall in mortality was associated with a more intensive intravenous therapy and with a reduction in the time from onset of the attack until surgery. Each of these factors may have influenced the mortality results. There was, however, a limited number of patients and the difference in mortality could be due to chance. About half of the patients went into remission in each of the two periods. This is a similar proportion of success of medical treatment as reported elsewhere (5, 6, 10). In the second period, corticosteroids were given to a larger proportion than in the first
45
period, and total parenteral nutrition was given routinely only in the second period. Apparently this change in regimen did not result in alteration of the remission rate. Nevertheless one cannot exclude that the number of patients who went into remission was influenced by the tendency to operate earlier in the second period. Parenteral nutrition in severe ulcerative colitis can provide adequate nutrition (1) and be of value in preparing the patients for the trauma of colectomy (3). I t is, however, uncertain whether such treatment can induce a remission. In this material there was no change of the remission rate after introduction of parenteral nutrition. Improvement of the colitis on such treatment appears to be the exception rather than the rule (3, 4). Nevertheless Solassol et a1 (8) reported that remission was obtained and surgery avoided in 6 out of 12 patients receiving total intravenous nutrition without the addition of steroids. The value of using steroids in acute severe colitis is disputed. I t is possible that steroids may promote remission in severe colitis (6, 9, 10). Nevertheless the effect of corticosteroids on the fatality rate in severe attacks appeared to be less than in moderate attacks (2)) and in two recent publications (6, 10) steroid treatment in severe colitis was associated with an overall mortality above 10%. A controlled trial may be necessary to show whether steroids have a place in the treatment of severe colitis. Early surgical treatment of severe attacks has been associated with a reduced fatality rate (4,5), and the tendency to earlier surgery in the period 1971 -1975 in the present series may have contributed to the reduced mortality together with improved parenteral nutrition. Comparing two materials composed of individuals drained from the same area but at two different periods is inferior to a controlled trial, which would be the ideal way to encircle the optimal treatment of ulcera-
46
H. Schjmsby, P. Heimann, D. Kremer, K. Nordgird, T. S. Raugstad, F. Ringheim and 0. Stray
tive colitis. (7) Essential for comparability is the age of the patients, the extension of the disease, the length of the history prior to attack, and severity of the attack, since these parameters are known to influence the prognosis (2, 11). The two materiaIs show a different age distribution with a larger number of patients under 20 years in the first period (Table I), but the proportion of patients above 40 years was nearly the same in the periods, (mortality is known to increase in elder patients). The extent of the disease (Table 11) as well as the length of the history before the attack were similar in the two periods. Furthermore, important parameters of the disease activity had nearly the same value in the two periods.
4.
5.
6.
7.
8.
9. REFERENCES 1. Dudrick, S. J. & Ruberg, R. L.: Principles and practice of parenteral nutrition. Gastroenterology 61: 901, 1971. 2. Edwards, F. C. & Truelove, S. C. :The course and and prognosis of ulcerative colitis. Gut 4: 299, 1963. 3. Fischer, J. E., Foster, G. S., Abel, R. M., Abbot, W. M. & Ryan, J. A.: Hyperalimentation as
10.
11.
therapy for inflammatory bowel disease. Am J Surg 125: 165, 1973. Flatmark, A., Fretheim, B. & Gjone, E.: Early colectomy in severe ulcerative colitis. Scand J Gastroenterol 10: 427, 1975. Goligher, J. C., Hoffmann, D. C. & De Dombal, F. T.: Surgical treatment of severe attacks of ulcerative colitis, with special reference to the advantages of early operation. Br Med J 4: 703, 1970. Kristensen, M., Kondahl, G., Fischermann, K. & Jarnum, S.: High dose prednisone treatment in severe ulcerative colitis. Scand J Gastroenterol 9 : 177, 1974. Riis, P.: Therapeutic influence on the prognosis of ulcerative colitis. Scand J Gastroenterol 9: 1, 1974. Solassol, E., Joyeux, H., Pujol, H., Balmes, J-L., Cayrol, B. & Favier, C. : Hypernutrition parenttrale substitutive et rectocolites graves. Arch Fr Ma1 App Dig 63: 115, 1974. Truelove, S. C. & Witts, L. J.: Cortisone in ulcerative colitis. Final report on a therapeutic trial. Br Med J 2 : 1041, 1955. Truelove, S. C. & Jewell, D. P.: Intensive intravenous regimen for severe attacks of ulcerative colitis. Lancet 1: 1067, 1974. 1974. Watts, J. McK., De Dombal, F. T., Watkinson, G. & Goligher, J. C.: Early course of ulcerative colitis. Gut 7: 16, 1966.
