Nutritional Studies

Among patients with complaints of diarrhea or constipation in whom no organic basis for their symptoms could be identified and no "wasting diseases" were diagnosed, 8 were selected (6 with constipation, 2 with diarrhea) as suitable subjects for determining the effects of long-term administration of polycarbophil on nutrition. Subjects were given 5 g of polycarbophil daily for periods ranging from 4 to 11 months, averaging 6 months. In this small group, no clinical or laboratory evidence of impaired nutrition could be found at the termination of drug administration. However, no demographic data were given, nor indications of what evaluations formed the basis for the conclusions. No comment was made regarding an evaluation of compliance.

Laxative/Enema-Dependent Bedridden Patients

Institutionalized patients, especially those confined to bed because of neurological disorders, are plagued w代h chronic constipation and obstipation. Indeed, many patients require constant medication with laxatives and the administration of frequent enemas requiring extensive nursing care. Fecal impactions are frequent and distasteful, both to patient and professional personnel. Such patients represent the severest test for laxative agents, particularly those of the bulk-forming type.

In a study of 37 hospitalized, bedridden patients polycarbophil was administered in doses of 1.5 to 4 g daily for 3 weeks to several months.⁶ In 23 of the patients (66%) an improvement in bowel function was noted. Removal of fecal material by enema or manipulation was facilitated, and patients progressed to less frequent impactions and to spontaneously-passed bowel movements. However, only 5 of 10 patients treated with a daily dose of 3 g or less responded favorably. Four g of resin were given daily to 31 subjects (including 4 patients previously studied with the smaller dose), and 22 (71%) responded in a satisfactory manner. Some patients failed to receive adequate doses of medication in a timely manner or received potent analgesics that depressed bowel function; when these cases were excluded, it was concluded the resin was effective in 82% of the patients.

This study was of an open, unblinded format; the patients, however, did serve as their own controls. No demographic data were presented, and no information concerning concomitant diagnoses, concurrent medications, dietary and fluid intakes, etc., were provided. Effectiveness was apparently based on subjective impressions of the nursing staff; no data regarding frequency of stooling, consistency, or other measurements were reported.

Laxative/Enema-Dependent Ambulatory Patients

A group of 37 ambulatory patients, 36 of whom

required laxatives or enemas for any bowel evacuation, was studied.⁶ When daily doses of 1.35 to 1.8 g of polyacrylic resin were given (in divided doses), slightly more than 35% of the subjects showed relief from constipation. This improved to 77% when a total daily dose of 2.7 to 4.0 g of resin was given in divided doses. The administration of resin "apparently" did not interfere with the absorption of drugs required for treatment of concurrent medical problems. Satisfactory bowel responses were apparent only after several days' on the medication, which caused the patients' desire to continue the medication to be poor and resulted in variable patient acceptance. In a group of 15 patients who responded to the resin by having a daily bowel evacuation without the use of other laxatives or enemas, continued improved bowel evacuatory patterns were observed even when the dosage of resin was decreased (13 patients) or discontinued (2 patients). Demographic data, concomitant diagnoses, concurrent medication, dietary and fluid intake, bowel frequency, endpoints of "successful" treatment, etc., were not reported in this study.

Chronic Constipation

Ten men and 16 women, ranging in age from 29 to 79 years had chronic constipation related to irritable colon syndrome (13), simple constipation (4), enforced bedrest (8), and idiopathic cryptic steatorrhea (1). These patients were selected because of a complaint of constipation, frequent use of laxatives or enemas, or failure to have a bowel movement at least once every three days. Intake of food and liquid was recorded. Polycarbophil or psyllium mucilloid was given double-blind in a daily dose of 5 g divided into 2 equal parts administered at 12-hour intervals with 8 ounces of water; the medication was continued for 2 weeks. Some subjects took both agents at different times so that comparisons could be made.

Eighty percent of patients receiving polycarbophil reported increased stool frequency, changing from 1 evacuation every 4 days (range, 2 to 7 days) to an average of 1 spontaneously passed bowel movement per day (range, 1 to 4 days); the same group reported improvement in stool consistency (75%), greater ease of stool passage (about 66%), and an increase in fecal volume (58%). Sixty-three percent of patients receiving psyllium mucilloid reported increased fecal frequency, and about 50% reported improvement in the other parameters.

Subjective impressions of both patients and physicians were combined; 79% of patients felt polycarbophil was superior to psyllium mucilloid, 14% reported the two agents equal in effectiveness, and 7% thought psyllium mucilloid gave superior relief. Side effects with both medications were minimal. No information on the relation of dietary and fluid intakes to bowel evacuation was reported.

Acute Diarrhea

Two studies in children with acute diarrhea have been published.¹³'¹⁴ A problem in such studies is that this very common malady is usually self-limiting within 72 hours of onset. Thus, an important but poorly controlled variable is the point along the natural time course where the patient enters the treatment protocol. This problem is somewhat compensated for by inclusion of only those patients who present with a defined increase in stool frequency. The natural course of this common symptom complex precludes the possibility of cross over studies; most evaluations are therefore parallel evaluations of two or more drugs.

In the first study,¹⁴ 67 children, ranging in age from 6 weeks to over 12 years (average approximately 3 years), were, when initially seen, passing 4 or more watery stools per day. They were evaluated with a double-blind protocol. The diarrheal state was associated with infections of the respiratory tract or acute gastroenteritis. No differentiation between viral and bacterial etiologies of the diarrhea was made. Patients were placed on a conventional dietary regimen for diarrhea, namely, solid foods proscribed and clear liquids orally for the first 24-hour period; low residue foods (skimmed milk, gelatin, apple sauce, banana) were permitted as tolerated during the second 24-hour period, with gradual resumption thereafter of the usual diet. Calcium polycarbophil or kaolin-pectin suspensions were dispensed in random sequence. The dosage, depending on the age of the patient, ranged from % teaspoonful three times to 2 teaspoonfuls four times daily. This gave a dosage range for calcium polycarbophil of 0.6 to 3.2 g daily, and for kaolin- pectin of 1.45 g kaolin, 0.0325 g pectin to 7.54 g kaolin, 0.169 g pectin, daily. Antidiarrheal effectiveness was compared in terms of the time between the beginning of treatment and the point when the stools became substantially or completely normal in consistency and frequency; the result was judged excellent if the diarrhea ceased within 24 hours; good, within 24 to 48 hours; fair, within 48 to 72 hours; poor, diarrhea uncontrolled within 72 hours. Effective control of diarrhea within 48 hours was observed in 68% of the children given calcium polycarbophil, and in 31% of those who received kaolin-pectin; 8% of the polycarbophil group failed to respond within 72 hours, while 28% failed to respond within 72 hours in the kaolin-pectin group. No sex distribution was reported, and no mention of the degree of compliance with the recommended dietary and medication schedules was noted; this becomes especially relevant in assessing the group

of patients who failed to respond within 72 hours. No data with respect to stool water content were given.

In a similarly designed study,¹³ which appears to be an expansion of the above study and incorporates previously reported results, 224 outpatient children were evaluated on the response of their diarrheal symptoms to calcium polycarbo- phil (127 children) or kaolin-pectin (97 children) suspensions. Ages of the patients ranged from birth to 18 years. Definition of intensity of diarrhea, medications, dietary recommendations, and end goals were the same as in the previously described study.

The calcium polycarbophil group consisted of a somewhat larger percentage of children below 1 year and greater than 5 years of age in comparison to the kaolin-pectin group; of the calcium polycarbophil group, more than 76% had severe and very severe symptoms, while about 71% of the kaolin-pectin group fell into these categories. Control of diarrheal symptoms within 48 hours of initiating treatment was achieved in 72% of those receiving calcium polycarbophil, while only 46% of the kaolin-pectin-treated patients improved in a similar manner. This difference was statistically significant.

Age and sex distributions were not correlated. No mention is made of the length of time symptoms had been present at the time treatment was initiated. Compliance was not described.