J
Chron Dis 1976, Vol. 29, pp. 59-63. Pergamon
Press. Printed in Great Britain
DIOCTYL SODIUM SULFOSUCCINATEAN TNEFFECTIVE PROPHYLACTIC LAXATIVE JAY GOODMAN,JANEPANG and ALICE N. BERGMAN Diabetes Service, Ranch0 Los Amigos Hospital, Downey, CA 90242 (Received 25 November 1974) Abstract-The effectiveness of dioctyl sodium sulfosuccinate (DSS) in preventing constipation was evaluated in a group of elderly patients on a general medical ward. On admission, 34 patients were randomized to a treatment group (200 mg DSS daily) or a control group and followed for a total of 876 at-risk days. The frequency and quality of stools were compared by standard student t-test analysis for days at risk and per patient. No statistically significant difference was found in the objective variables of frequency or quality of stools. We conclude that routine ‘prophylactic bowel medication’ (200 mg DDS) is not effective in altering the incidence of constipation in our hospital setting. INTRODUCTION IT IS routine
practice in many hospital settings to empirically administer ‘prophylactic bowel medication’ in an effort to avoid constipation during hospitalization. These drugs are generally ‘over the counter’ preparations with varying degrees of proven efficacy. Dioctyl Sodium Sulfosuccinate (DSS) is the drug most frequently used in our hospital for this purpose. A search of the literature reveals no controlled study to document the effectiveness of routine ‘prophylaxis’ with DSS to prevent constipation. For this reason we designed a randomized prospective study to evaluate whether the routine use of 200 mg DSS daily actually altered the incidence of constipation in our geriatric hospital setting. METHODS
Thirty-four consecutive patients admitted to the Ranch0 Los Amigos Hospital Chronic Medical Service were prospectively assigned by a flip of a coin to a ‘prophylactic bowel management program’ or to a control group which did not receive any type of laxative. Those patients randomized to the bowel program received either dioctyl sodium sulfosuccinate (Doxinate, Hoechst, Pharmaceuticals New Jersey) 100 mg twice daily, or a comparable dose of dioctyl sodium sulfosuccinate elixir (CoIace, Mead Johnson, Indiana) 30 ml twice daily depending upon their ability to swallow medications. If after two days a patient in the treatment group did not have a bowel movement, he received either bisacodyl NF (Dulcolax, Hoehring Ingelheim Ltd., New York) or glycerin suppositories on the evening of the third day. Failing this therapy, the patient would receive a sodium biphosphate and sodium phosphate enema (Fleet Enema, Fleet Co., Virginia). Failing these measures, no additional therapy was instituted. The study was conducted from March 1974 until June 1974 (3 months) 59
JAY GOODMAN,JANE PANG and ALICE N. BE~WAN
60
and included all new admissions to the service with the following exclusions: patients with spinal cord injuries, acute myocardial infarction, or those specifically admitted because of diarrhea. Twenty-one of these 34 study patients had severe central nervous system disability resulting from cerebral vascular accidents or contusions. The remaining patients had the following primary diagnoses: decubitus ulcer, diabetes, rheumatoid arthritis, prostatic carcinoma, alcoholism, arteriosclerotic peripherial vascular disease, tuberculosis and anorexia nervosa. Stools were graded by the nursing staff as follows: (A) Watery, liquid; (B) Soft formed, normal stool; (C) Watery, hard formed stool; (D) Hard, dry stool; (E) Enema evacuated stool; or (F) Manually evacuated stool. Daily activity was graded as follows: (0) Bed bound ; (1) Wheelchair restricted; or (2) Walking. Constipation was evaluated by analyzing the number of days between bowel movements and the quality of each bowel movement. Comparison of groups was achieved by standard student t-test analysis and was performed both by days at risk and per patient in each group. All patients were managed clinically by their primary care physician with the exception of their bowel management, which was dictated by protocol. RESULTS
The patients’ age, mean level of activity and days observation were comparable for the two groups as was the spectrum of their clinical diagnoses: TABLE1 No. of Pts
Age (%SEM)
Activity
Comatose
Days
Treated
17
53.05 st4.42
0.58kO.17
7
25.9444.32
Untreated
17
59.68f4.54
0.61 *I-o.18
6
255816.18
Their diets were similar. TABLE2 Regular or puree
Tube feeding preparations* Milk based* Meat based7
Treated
12
3
2
Untreated
12
3
2
*Protein/Fat/Carbohydrate/cc 0.07 g/cc/O.03 g/cc 0.18 g/cc, 1.3 cal/cc. Vrotein/Fat/Carbohydrate/cc 0.07 g/cc/O.03 g/cc/O. 14 g/cc, 1.1 cal/cc. *Liquid diet formulas Div. of Hospital Diet Products Corp. Buena Park.
The mean number of stools per patient and frequency of stool per patient days were comparable (Table 3). Similarly all character of stools (A, B, C, D, E, and F) were comparable for the two groups. No patient in either group required manual evacuation (F). Analysis of the number of at risk days between bowel movements (Table 4) shows that the treated rather than the untreated patients had nearly twice the incidence of missing one day (p < 0.05). However the incidence of missing one day was similar in both groups when evaluated per patient. The frequency of missing two, three, four and five days between bowel movements was similar per patient or per risk days for the two groups.
Dioctyl Sodium Sulfosuccinate-An
Ineffective Prophylactic
Laxative
61
TABLE 3. BOWEL MOVEMENTS
Treated + SEM
Mean Days per patient
25.94*
Bowel movements/patient Bowel movements/patient
day x 100 %
(A) Watery liquid stool/patient Watery liquid stool/patient
day
(B) Soft formed normal stool/patient Soft formed normal stool/patient day (C) Watery hard formed stool/patient Watery hard formed stool/patient (D) Hard, dry stool/patient Hard, dry stool/patient
day
(E) Enema evacuated stool/patient Enema evacuated stool/patient (F)
day
day
Manually evacuated stool/patient
4.31
Untreated Mean & SEM 25.58
6.18
26.11* 86.64 %
5.82 11.17%
23.76 81.47%
6.28 11.67%
3.60* 19.567:
0.99 7.76
9.64 32.00 %
3.85 9.65
21.58* 66.41%
5.52 10.65
13.05 48.47 %
3.32 8.0
0.64* 2.50%
0.41 1.51
0.05 0.1%
0.05 0.1
0.17* 0.70 %
0.05 0.42
1.23 3.35 %
1.45 1.45
0.47* 1.23%
0.24 0.59
0.11 1.17%
0.08 1.0
0
0
TABLE 4. INCIDENCE OF DAYS BETWEEN BOWEL MOVEMENTS
Mean No. of times 1 day elapsed without a bowel movement/patient No. of times 1 day elapsed without a bowel movement/patient day x 100% No. of times 2 days elapsed without a bowel movement/patient No. of times 2 days elapsed without a bowel movement/patient day No. of times 3 days elapsed without a bowel movement/patient No. of times 3 days elapsed without a bowel movement/patient day No. of times 4 days elapsed without a bowel movement/patient No. of times 4 days elapsed without a bowel movement/patient day No. of times 5 days elapsed without a bowel movement/patient No. of times 5 days elapsed without a bowel movement/patient day No. of times more than 5 days elapsed without a bowel movement *=p=n.s. t=z= 1.90, p < 0.05.
Treated It SEM
3.29*
Untreated Mean k SEM
0.64
2.88
i-
0.95
1.50
8.53% &
2.35
1.17*
0.33
1.35
0.52
10.35 %*
4.41
8.58%
3.08
0.64*
0.22
0.82
0.32
2.35 %*
0.84
4.05 %
1.30
0.05*
0.05
0.23
0.13
0.23 %*
0.23
1.17%
0.63
0.05*
0.05
1.47x*
1.17
14.29%.tf
0*
&
62
JAY GOODMAN,
JANE PANG and ALICE N. BFSSMAN DISCUSSION
Dioctyl sodium sulfosuccinate is an anionic surfactant widely used as a stool softener [l]. In rats, DSS not only increases the hydration of colonic contents but inhibits gastric emptying and thereby slows total transit time of a dye meal [2]. In a clinical trial where 300 mg DSS was administered to elderly constipated patients (2.47kO.21 stools/week) in a double-blind crossover study, Hyland and Foram [3] report 35 per cent more stools/week and an improvement in 12 of their 15 patients. In the present study, we were unable to demonstrate a statistically significant (p < 0.05) difference between patients receiving 200 mg DSS daily and control patients with respect to frequency or quality of stool. Our patients were not initially considered to be ‘constipated’; none went on to become constipated; and no patient in either group required manual stool evacuation. We were unable to correlate diet with stool frequency or quality. Our data document the lack of effect in objectively measured parameters (quality and frequency of stools) in comparable groups treated with and without DSS. This is in direct contradiction to a number of subjective anecdotal reports [4-71 attesting to the value of DSS in a variety of clinical settings. The interpretation of this negative report has direct application in routine inpatient hospital management. Although it is justified to try to avoid constipation, the use of DSS was an ineffective mode of therapy in our setting. The reasons for its lack of effect in our setting may stem from one of the following: (1) an inadequate dosage of DSS (2) an inappropriate patient group or setting or (3) the basic ineffectiveness of the drug itself in preventing constipation. The only data pertinent to the appropriate dosage of DSS is found in the manufacturers’ package insert where 50-240 mg daily is the mentioned adult dosage range. Since our patients all received 200 mg daily (nearly the maximum recommended dosage) it is unlikely that they received an inadequate amount as defined by the present recommendations and usage. The patient group is particularly representative of the patients usually felt to be prone to impaction. They were elderly, debilitated, and usually bed bound. By the same token, they were the least likely to benefit from a placebo effect since the majority of our patients were either comatose or disoriented and confused. For these reasons we feel our population and setting offered an ideal environment to evaluate any drug designed to prevent constipation. Whether the drug actually offers anything beyond a placebo effect in preventing constipation is in doubt, although the issue of appropriate dosage must first be resolved. Clearly, 200 mg DSS daily, in addition to a regular diet, offers no advantage over diet alone. Whether a greater dose offers any advantage remains to be determined. The role of diet in maintaining bowel regularity may be crucial in any study. Our overall low incidence of constipation may reflect the diet which, by itself, was adequate to normalize these patients. If diet alone is usually sufficient to regulate a patient, then any additional effect of a laxative drug may be masked and unnecessary. REFERENCES 1. 2.
Darlington RC: Laxatives. In Handbook of Non Prescription Drugs. Grittenhagen, Hawkins (Eds.) American Pharmaceutical Association, 1971, p. 54 Lish PM: Some pharmacological effects of dioctyl sodium sulfosuccinate on the gastrointestinal tract of the rat. Gastroenterology 41: 580-584, 1961
Dioctyl Sodium Sulfosuccinate-An 3. 4. 5. 6. 7.
Ineffective Prophylactic
Laxative
63
Hyland CM, Foram JD: Dioctyl sodium sulfosuccinate as a laxative in the elderly. Practitioner 200: 698-699, 1968 Harris R: Constipation in geriatrics management with dioctyl sodium sulfosuccinate. Am J Digestive Dis 9: 487-492, 1957 Bernard LI, Jarolim C, Tumoneng L: Prevention and treatment of constipation during pregnancy. OB/Gyn Digest 7: 47-50, 1965 Malow L, Spiesman M: Postoperative anorectal surgery a clinical evaluation of a new compound. Geo Pratt 25 : 9-l 1, 1962 Dennison AD: Use of dioctyl sodium sulfosuccinate in cardiovascular disease correction of bowel function. Am J Cardlol 1: 400403, 1958
Chron Dis 1976, Vol. 29, pp. 59-63. Pergamon
Press. Printed in Great Britain
DIOCTYL SODIUM SULFOSUCCINATEAN TNEFFECTIVE PROPHYLACTIC LAXATIVE JAY GOODMAN,JANEPANG and ALICE N. BERGMAN Diabetes Service, Ranch0 Los Amigos Hospital, Downey, CA 90242 (Received 25 November 1974) Abstract-The effectiveness of dioctyl sodium sulfosuccinate (DSS) in preventing constipation was evaluated in a group of elderly patients on a general medical ward. On admission, 34 patients were randomized to a treatment group (200 mg DSS daily) or a control group and followed for a total of 876 at-risk days. The frequency and quality of stools were compared by standard student t-test analysis for days at risk and per patient. No statistically significant difference was found in the objective variables of frequency or quality of stools. We conclude that routine ‘prophylactic bowel medication’ (200 mg DDS) is not effective in altering the incidence of constipation in our hospital setting. INTRODUCTION IT IS routine
practice in many hospital settings to empirically administer ‘prophylactic bowel medication’ in an effort to avoid constipation during hospitalization. These drugs are generally ‘over the counter’ preparations with varying degrees of proven efficacy. Dioctyl Sodium Sulfosuccinate (DSS) is the drug most frequently used in our hospital for this purpose. A search of the literature reveals no controlled study to document the effectiveness of routine ‘prophylaxis’ with DSS to prevent constipation. For this reason we designed a randomized prospective study to evaluate whether the routine use of 200 mg DSS daily actually altered the incidence of constipation in our geriatric hospital setting. METHODS
Thirty-four consecutive patients admitted to the Ranch0 Los Amigos Hospital Chronic Medical Service were prospectively assigned by a flip of a coin to a ‘prophylactic bowel management program’ or to a control group which did not receive any type of laxative. Those patients randomized to the bowel program received either dioctyl sodium sulfosuccinate (Doxinate, Hoechst, Pharmaceuticals New Jersey) 100 mg twice daily, or a comparable dose of dioctyl sodium sulfosuccinate elixir (CoIace, Mead Johnson, Indiana) 30 ml twice daily depending upon their ability to swallow medications. If after two days a patient in the treatment group did not have a bowel movement, he received either bisacodyl NF (Dulcolax, Hoehring Ingelheim Ltd., New York) or glycerin suppositories on the evening of the third day. Failing this therapy, the patient would receive a sodium biphosphate and sodium phosphate enema (Fleet Enema, Fleet Co., Virginia). Failing these measures, no additional therapy was instituted. The study was conducted from March 1974 until June 1974 (3 months) 59
JAY GOODMAN,JANE PANG and ALICE N. BE~WAN
60
and included all new admissions to the service with the following exclusions: patients with spinal cord injuries, acute myocardial infarction, or those specifically admitted because of diarrhea. Twenty-one of these 34 study patients had severe central nervous system disability resulting from cerebral vascular accidents or contusions. The remaining patients had the following primary diagnoses: decubitus ulcer, diabetes, rheumatoid arthritis, prostatic carcinoma, alcoholism, arteriosclerotic peripherial vascular disease, tuberculosis and anorexia nervosa. Stools were graded by the nursing staff as follows: (A) Watery, liquid; (B) Soft formed, normal stool; (C) Watery, hard formed stool; (D) Hard, dry stool; (E) Enema evacuated stool; or (F) Manually evacuated stool. Daily activity was graded as follows: (0) Bed bound ; (1) Wheelchair restricted; or (2) Walking. Constipation was evaluated by analyzing the number of days between bowel movements and the quality of each bowel movement. Comparison of groups was achieved by standard student t-test analysis and was performed both by days at risk and per patient in each group. All patients were managed clinically by their primary care physician with the exception of their bowel management, which was dictated by protocol. RESULTS
The patients’ age, mean level of activity and days observation were comparable for the two groups as was the spectrum of their clinical diagnoses: TABLE1 No. of Pts
Age (%SEM)
Activity
Comatose
Days
Treated
17
53.05 st4.42
0.58kO.17
7
25.9444.32
Untreated
17
59.68f4.54
0.61 *I-o.18
6
255816.18
Their diets were similar. TABLE2 Regular or puree
Tube feeding preparations* Milk based* Meat based7
Treated
12
3
2
Untreated
12
3
2
*Protein/Fat/Carbohydrate/cc 0.07 g/cc/O.03 g/cc 0.18 g/cc, 1.3 cal/cc. Vrotein/Fat/Carbohydrate/cc 0.07 g/cc/O.03 g/cc/O. 14 g/cc, 1.1 cal/cc. *Liquid diet formulas Div. of Hospital Diet Products Corp. Buena Park.
The mean number of stools per patient and frequency of stool per patient days were comparable (Table 3). Similarly all character of stools (A, B, C, D, E, and F) were comparable for the two groups. No patient in either group required manual evacuation (F). Analysis of the number of at risk days between bowel movements (Table 4) shows that the treated rather than the untreated patients had nearly twice the incidence of missing one day (p < 0.05). However the incidence of missing one day was similar in both groups when evaluated per patient. The frequency of missing two, three, four and five days between bowel movements was similar per patient or per risk days for the two groups.
Dioctyl Sodium Sulfosuccinate-An
Ineffective Prophylactic
Laxative
61
TABLE 3. BOWEL MOVEMENTS
Treated + SEM
Mean Days per patient
25.94*
Bowel movements/patient Bowel movements/patient
day x 100 %
(A) Watery liquid stool/patient Watery liquid stool/patient
day
(B) Soft formed normal stool/patient Soft formed normal stool/patient day (C) Watery hard formed stool/patient Watery hard formed stool/patient (D) Hard, dry stool/patient Hard, dry stool/patient
day
(E) Enema evacuated stool/patient Enema evacuated stool/patient (F)
day
day
Manually evacuated stool/patient
4.31
Untreated Mean & SEM 25.58
6.18
26.11* 86.64 %
5.82 11.17%
23.76 81.47%
6.28 11.67%
3.60* 19.567:
0.99 7.76
9.64 32.00 %
3.85 9.65
21.58* 66.41%
5.52 10.65
13.05 48.47 %
3.32 8.0
0.64* 2.50%
0.41 1.51
0.05 0.1%
0.05 0.1
0.17* 0.70 %
0.05 0.42
1.23 3.35 %
1.45 1.45
0.47* 1.23%
0.24 0.59
0.11 1.17%
0.08 1.0
0
0
TABLE 4. INCIDENCE OF DAYS BETWEEN BOWEL MOVEMENTS
Mean No. of times 1 day elapsed without a bowel movement/patient No. of times 1 day elapsed without a bowel movement/patient day x 100% No. of times 2 days elapsed without a bowel movement/patient No. of times 2 days elapsed without a bowel movement/patient day No. of times 3 days elapsed without a bowel movement/patient No. of times 3 days elapsed without a bowel movement/patient day No. of times 4 days elapsed without a bowel movement/patient No. of times 4 days elapsed without a bowel movement/patient day No. of times 5 days elapsed without a bowel movement/patient No. of times 5 days elapsed without a bowel movement/patient day No. of times more than 5 days elapsed without a bowel movement *=p=n.s. t=z= 1.90, p < 0.05.
Treated It SEM
3.29*
Untreated Mean k SEM
0.64
2.88
i-
0.95
1.50
8.53% &
2.35
1.17*
0.33
1.35
0.52
10.35 %*
4.41
8.58%
3.08
0.64*
0.22
0.82
0.32
2.35 %*
0.84
4.05 %
1.30
0.05*
0.05
0.23
0.13
0.23 %*
0.23
1.17%
0.63
0.05*
0.05
1.47x*
1.17
14.29%.tf
0*
&
62
JAY GOODMAN,
JANE PANG and ALICE N. BFSSMAN DISCUSSION
Dioctyl sodium sulfosuccinate is an anionic surfactant widely used as a stool softener [l]. In rats, DSS not only increases the hydration of colonic contents but inhibits gastric emptying and thereby slows total transit time of a dye meal [2]. In a clinical trial where 300 mg DSS was administered to elderly constipated patients (2.47kO.21 stools/week) in a double-blind crossover study, Hyland and Foram [3] report 35 per cent more stools/week and an improvement in 12 of their 15 patients. In the present study, we were unable to demonstrate a statistically significant (p < 0.05) difference between patients receiving 200 mg DSS daily and control patients with respect to frequency or quality of stool. Our patients were not initially considered to be ‘constipated’; none went on to become constipated; and no patient in either group required manual stool evacuation. We were unable to correlate diet with stool frequency or quality. Our data document the lack of effect in objectively measured parameters (quality and frequency of stools) in comparable groups treated with and without DSS. This is in direct contradiction to a number of subjective anecdotal reports [4-71 attesting to the value of DSS in a variety of clinical settings. The interpretation of this negative report has direct application in routine inpatient hospital management. Although it is justified to try to avoid constipation, the use of DSS was an ineffective mode of therapy in our setting. The reasons for its lack of effect in our setting may stem from one of the following: (1) an inadequate dosage of DSS (2) an inappropriate patient group or setting or (3) the basic ineffectiveness of the drug itself in preventing constipation. The only data pertinent to the appropriate dosage of DSS is found in the manufacturers’ package insert where 50-240 mg daily is the mentioned adult dosage range. Since our patients all received 200 mg daily (nearly the maximum recommended dosage) it is unlikely that they received an inadequate amount as defined by the present recommendations and usage. The patient group is particularly representative of the patients usually felt to be prone to impaction. They were elderly, debilitated, and usually bed bound. By the same token, they were the least likely to benefit from a placebo effect since the majority of our patients were either comatose or disoriented and confused. For these reasons we feel our population and setting offered an ideal environment to evaluate any drug designed to prevent constipation. Whether the drug actually offers anything beyond a placebo effect in preventing constipation is in doubt, although the issue of appropriate dosage must first be resolved. Clearly, 200 mg DSS daily, in addition to a regular diet, offers no advantage over diet alone. Whether a greater dose offers any advantage remains to be determined. The role of diet in maintaining bowel regularity may be crucial in any study. Our overall low incidence of constipation may reflect the diet which, by itself, was adequate to normalize these patients. If diet alone is usually sufficient to regulate a patient, then any additional effect of a laxative drug may be masked and unnecessary. REFERENCES 1. 2.
Darlington RC: Laxatives. In Handbook of Non Prescription Drugs. Grittenhagen, Hawkins (Eds.) American Pharmaceutical Association, 1971, p. 54 Lish PM: Some pharmacological effects of dioctyl sodium sulfosuccinate on the gastrointestinal tract of the rat. Gastroenterology 41: 580-584, 1961
Dioctyl Sodium Sulfosuccinate-An 3. 4. 5. 6. 7.
Ineffective Prophylactic
Laxative
63
Hyland CM, Foram JD: Dioctyl sodium sulfosuccinate as a laxative in the elderly. Practitioner 200: 698-699, 1968 Harris R: Constipation in geriatrics management with dioctyl sodium sulfosuccinate. Am J Digestive Dis 9: 487-492, 1957 Bernard LI, Jarolim C, Tumoneng L: Prevention and treatment of constipation during pregnancy. OB/Gyn Digest 7: 47-50, 1965 Malow L, Spiesman M: Postoperative anorectal surgery a clinical evaluation of a new compound. Geo Pratt 25 : 9-l 1, 1962 Dennison AD: Use of dioctyl sodium sulfosuccinate in cardiovascular disease correction of bowel function. Am J Cardlol 1: 400403, 1958
