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2 THERAPY FOR DIARRHEA ORAL REHYDRATION THERAPY Death associated with acute diarrhea is most often due to the dehydration that results from the loss of body water and electrolytes in the stool. Lost water and electrolytes can usually be replaced orally, and few cases require intravenous therapy to prevent serious complications or death. Because deficits of similar size can occur whether diarrhea is associated with bacteria or with viruses, treatment depends more on the size of the deficit than on the specific type of diarrhea or other characteristics of the patient. Thus, it is possible to use similar hydration solutions in persons with different types of diarrhea and of different ages. Dehydrated children who are not in shock and who are able to drink should be rehydrated orally. The value of oral Dehydration therapy (ORT) in industrialized and developing countries has received considerable attention and has been well documented.l0,ll,36~37~43 The oral Dehydration solution formula recommended by the World Health Organization (WHO) contains, in millimols per liter, the following: sodium, 90; chloride, 80; potassium, 20; glucose, 111; and a base, such as citrate tribasic or bicarbonate, 30. The volume to be administered is that judged clinically to correct the estimated deficit. Once Dehydration is completed, hydration can be maintained during continuing diarrhea by alternating between the oral solution and water. Water can be provided by breast-feeding on demand or by 11

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giving plain water equal to about 50% of the volume of the oral solution administered (i.e., 2 parts ORT solution to 1 part water or breast milk). If the complete formula is not available, ORT solutions for treatment of diarrhea can be made with salt and a source of glucose found in the home. The source of glucose is usually crude or sometimes refined household sugar; other sources, such as properly prepared rice powder, appear to be better in facilitating the absorption of electrolytes and water. A number of recent studies have shown clear reductions in stool output and duration of diarrhea when rice powder (which contains glucose, amino acids, and oligopeptides)32~39 or soy44 is used as a substrate. It has been demonstrated that the addition of an amino acid, such as glycine, to the standard glucose-electrolyte oral Dehydration solution decreases duration of diarrhea and fecal fluid losses.34~38 Rice powder and other cereals (or soy) are theoretically advantageous, because they contain amino acids or carbohydrate (in the form of glucose chains), each of which promotes sodium transport. Additionally, because the glucose is in the form of starch, more can be given without increasing the osmolarity. The upper limit of starch content has not yet been defined. Because infants less than 6 months old have incomplete development of pancreatic amylase, it is not certain whether they can completely digest these starches. If an improved ORT solution containing multiple water-soluble, organic molecules becomes available, it could increase the absorption of sodium and water and decrease the diarrhea! volume and duration of diarrhea. The small proportion of patients who have severe dehydration and shock, or who are unable to drink, require immediate intravenous therapy. The intravenous fluid should be administered rapidly, to reverse shock within 1 hour and to correct the estimated volume deficit within 2-4 hours. It should contain enough potassium and base to correct hypokalemia and acidosis. Suitable intravenous Dehydration solutions, such as Ringer's lactate, have been described elsewhere.52 Maintenance with ORT solution is then begun. Persistent vomiting is often given as a reason for withholding ORT solutions, but vomiting usually stops in the first 4 hours if ORT solutions are used. - 12

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EFFECTS OF ORAL REHYDRATION THERAPY ON NUTRITIONAL STATUS Initial clinical observations found that children receiving oral Dehydration solutions often wanted to eat within hours of the correction of fluid and electrolyte depletion.33 That finding suggested that ORT could have an additional benefit on nutritional status. This potential benefit has now been examined in at least seven studies of children with diarrhea (reviewed in Hirschhornl7~. In these studies, nutritional status was measured, and continued feeding was urged for children treated either with or without ORT solutions. Children receiving the oral rehydration solution showed significantly greater gains in weight than children not receiving the solution; the difference persisted over time, even though not all gained weight at normal rates. The mean monthly increment in weight in the oral dehydration solution-groups was 70 g more than that in the non-oral dehydration solution groups. These results suggest that ORT programs can result in nutritional benefit when oral rehydration solution is combined with feeding. Such programs would be expected to be most effective where the current practice is to withhold food during illness. Other factors, such as the adequacy of a child's usual diet and the parent's ability to purchase food, will also influence the impact of ORT. NUTRITIONAL THERAPY The subcommittee recommends continued feeding during the active and early convalescent phases of diarrhea. The benefits to be expected vary with the nutritional quality of the foods offered, which can be increased by temporary fortification. Even the usual diet, however, is better than no food at all. The primary objective of feeding should always be to minimize the adverse effects of the illness on nutritional status. A secondary objective is to promote normal intestinal mucosal renewal and absorptive and digestive functions. The objectives of therapy are the same whether it is provided at home, in a community health clinic, or in a hospital. Although more complex - 13

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individualized dietary treatment might be available in a hospital, the therapeutic principles are similar in all settings. Feeding will not diminish the necessity to maintain fluid balance. Water and electrolytes must be included in the assessment of nutrient needs. As noted, proper Dehydration is the first therapeutic goal. Once normal hydration status is restored--usually within a few hours--dietary intake can resume. Ideal therapy provides the nutrients to meet the increased demands of illness and catch-up growth, in addition to the usual requirement for maintenance, growth, and physical activity. Choice of foods, mode of preparation, and frequency of feeding depend on the child's age, feeding history, and physiologic status. Particular attention should be given to the nutrient density of the food used, the quality of its carbohydrate and fat, the biologic value of its protein, and, if appropriate, its osmolarity. The need for specific nutrient supplements also must be considered. Cultural factors are particularly important determinants of the management of diarrhea. _ . . ~ c, _ . Withholding of food by a child s caretaker and failure to compensate for a decrease in food intake during illness by increasing feeding during convalescence are major contributors to the adverse nutritional effects of diarrhea. In addition to folk beliefs, medical advice often supports the withholding of particular foods during and after diarrhea. It will be difficult to change folk beliefs without first obtaining the support of the various medical practitioners in the community. Careful attention will need to be paid to this group. The development of specific protocols for the dietary management of acute diarrhea in different settings goes beyond the scope of this discussion. In some cases, specific questions will need to be answered and protocols tested before a diet is recommended. However, sufficient information is available to provide guidance that can be useful in the development of clinical protocols for all levels of care--home, community-based clinic, and hospital. - 14 -

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CHOICE OF FOODS Clear, pragmatic, and generally applicable sets of feeding recommendations need to be formulated for distinct sociocultural settings. In preparing such recommendations, it is important to understand the factors that affect food choices and target populations. Criteria for choosing diets to meet normal requirements and the additional needs for catch-up growth should include the nutrient composition and density of the foods, familiarity of the foods, and the possibility of complementary nutrient mixtures that maximize absorption, particularly that of carbohydrates. The development of specific feeding recommendations is constrained by cultural norms and practices, economic limitations, the availability of foods, and difficulty in preparing foods in the home. Although the immediate availability of specific foods and their costs usually are considered early in treatment, their continued availability and costs during the longer period of convalescence and catch-up growth are equally important. Food choices should be influenced by preillness feeding histories. For example, breast-feeding should be continued if possible. If a breast-fed child less than 6 months old is growing normally, it can be assumed that lactation is adequate and that nutritional deficits can be corrected with breast milk alone. Ideally, normal growth can be documented from measurements taken during routine examinations. If those data are not available, weight for length greater than the fifth percentile can be used as a crude indicator that breast milk is adequate. For infants older than 6 months with or without wasting, breast-feeding should be continued, but should be complemented with other foods. For the child who has been weaned from human milk, appropriate available weaning foods must be defined in each locale . The quality of the mixture of dietary proteins should be considered in selecting foods either to complement breast milk or to provide all a child's nutrient intake. Protein quality should be assessed on the basis of digestibility and the balance of essential amino acids, which are determinants of the efficiency with which the protein is used for maintenance and growth. Estimates of protein quality are found in - 15

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several reference documents, such as Energy and Protein Requirements.14~15 Animal protein generally is more digestible and of higher biologic quality than plant protein. However, processing techniques can be used to improve digestibility of vegetable protein, and proteins from different sources can be mixed to improve their combined food value. For example, the value of wheat-flour protein is inferior to that of casein, but their combination in approximately equal proportions (55% wheat, 45% casein) has a value equivalent to that of 100X casein; the protein value of a corn and black bean mixture (equal proportions) is substantially higher than that of either component; and the value of a mixture of corn and milk proteins (equal proportions) is higher than that of either component. Clinical and dietetic personnel must be encouraged to identify locally available foods that can be combined to increase food value economically. Allergenic proteins, such as those found in cow's milk, can easily cross a damaged intestinal mucosa and sensitize a child. However, the subcommittee believes that this risk is small, compared with the benefits of continued nutrient intake. Known sensitivity to specific foods contraindicates their use in dietary management in an individual case. On the basis of the fat-to-energy ratio of human milk,2 which is considered to provide an optimal combination of nutrients for an infant, the subcommittee suggests that fat should supply about 40-50% of dietary energy during the first 6 months of life and approximately 35-40% for the remainder of early childhood. As the fat content falls further and further below the recommended proportions, the quantity of food needed to supply appropriate amounts of energy becomes excessively large; that progression increases the risk that energy intake will be inadequate. Vegetable fats that include relatively high proportions of unsaturated fat or fats of medium chain length are recommended for the first 6 months of life and are preferred during the early phases of treatment for diarrhea, because they are generally more digestible and absorbable than highly saturated, long-chain fats.l3 Plant-seed oils (e.g., corn and soy) are relatively high in unsaturated fats, including the essential fatty acids. In contrast, coconut oil is more saturated and contains relatively - 16

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high proportions of medium-chain-length fats, but contains practically none of the essential fatty acids.1 Although sufficient information is not available to make specific recommendations, a combination of unsaturated fats and mixed long-chain saturated fats should lead to better absorption than saturated fats alone. Although malabsorption of fats does not appear to exacerbate diarrhea, it does prolong nutritional rehabilitation and adversely affects the retention of nitrogen when protein intake is marginal. Carbohydrates usually account for 35-55% of dietary energy during early infancy.3 The principal types of dietary carbohydrate are starches and the disaccharides sucrose and lactose. Although the feeding of lactose to infants with gastroenteritis might be considered unwise, because of the recognized loss of intestinal lactase activity during intestinal infection, this type of acquired lactase deficiency is seldom total. Lactose at a concentration equivalent to that of half-strength cow's milk is generally well tolerated in diarrhea, especially in mixed foods, such as milk and cereal combinations. Sucrose, the other major dietary disaccharide, and processed vegetable starches usually are easily digested and absorbed by children with diarrhea. The potentially adverse effects of dietary carbohydrate can be minimized by multiple feedings of small amounts of mixtures of carbohydrates. This strategy is the least likely to strain possibly decreased capacity for carbohydrate digestion. The potential for carbohydrate intolerance should be carefully addressed in clinical protocols prepared for primary health care workers. Misconceptions about transient intolerance to carbohydrate all too often lead to prolonged withholding of food. As a practical matter, if single challenges with lactose-containing foods do not aggravate clinical symptoms, continued tolerance during convalescence may be assumed. The selection of foods also requires the evaluation of bulk and nutrient concentrations relative to energy content. One must consider gastric capacity, number of feedings per day, and nutrient needs of the child. If the amount of food that meets estimated energy needs exceeds the expected gastric capacity, the diet is too bulky. Some examples of energy-bulk relationships are - 17

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shown in Table 1. Bulk can be reduced by increasing the fat content of the diet. Infections accompanied by vomiting or the consumption of foods with high osmolar- ity or fat content will slow gastric emptying and often decrease tolerance to bulk. To minimize these problems, frequent feedings (e.g., every 2-4 hours, depending on the age of the child) of smaller quantities are highly desirable. Estimates of the energy density necessary to meet energy requirements are shown in Table 2. Ideally, foods should provide twice the protein-to-calorie ratio that is normally required. No food is likely to satisfy this ratio for all essential nutrients at all ages, so supplementation or fortification with key nutrients might be needed for nutrient replenishment. Mixing of plant and animal foods often increases the nutrient-to-calorie ratio substantially. Diet manuals, such as Cameron and Hofvander's Manual for Feeding Infants and Young Children,9 and nutrition texts such as Latham's Human Nutrition in Tropical Africa,2 suggest specific, practical approaches for reducing food bulk and increasing nutrient density. Cameron and Hofvander9 include sample recipes that could be developed and tested for local use. When a child's clinical status does not permit the introduction of complex foods at the beginning of treatment, the addition of starches, cereal powders, proteins, amino acids, or small polypeptides to standard oral Dehydration solutions can be beneficial. Such additions might speed Dehydration by reducing stool volume and at the same time mitigate energy and protein deficits. If this feeding regimen is adopted, the child should be offered more complex foods within 12 hours. FOOD PREPARATION In addition to the nutritional concerns described above, preparation of food should consider consistency, digestibility, and acceptability. Dilute watery paps or soups and excessively bulky foods should be avoided as primary nutrient sources if possible. When formulated appropriately, watery paps or soups can be used as 18

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o :^ l - o^ al cat .~ a c' bo o .,' ~ ~ c. 3 v o o of o o o Cat Sit ~ en ~ 0 0 .~1 ~ ~ o_ ~ ~ ~ ,1 V4 ~ ~ ~ U ~ ~ o ~ of v At: ~ ~ sat a) o ~ =.- U) ~ ~ ~ ~ ~ ~ 3 a ~ ~ o ~ ~ ~ sit ~ O ~ 1 cat O C. ~ o 4, ~ .- o ~ ~ ~ V 0 ~ al cat . . . ~ e e ~ ~ ~ ~ ~ ~ ~ ~ ~ . ~ Z O Cut ~ ~ O .,, ~ ~~ - ~ V O ~ O ~ ~ .- [z3 ~ O ~ O ~ ~ ~q a) L~ ~ O U~ ~ ~ U. - ~ ^m ~ ~ ~ ~ ~ V E~ O O % ~ ~1 C) ~ ~ ~ ~ O ~ c) V O O .-l S~ O .,~ ^, ~ ~ P~ ~ V a,) 0 v O C~ - a "~ O ~ ~ . O ~ V ^ ~ - .,1 O a) ~ =~ 0 o~ = O >: ~ .- ~ O ~ ~ ~ ~ . O co V _' c~ ~ ~ a' ~ . - O C~ ~ ~ O ~e ~ ~e ~ ~ ~ ~ ~ 00 ~ O C) ~ b o e = - O ~- ~ m ~ c. ~ c~ u, :^ ~ = - O O O a1 c~ 0 0 u~ ~ 0 u~ - v ~ 0 c~ ~ ~ a, ~ ~ ~ ~ ~ ~ .~- . ~ ~ c~ ~ ~ ~ cn ~ =: ~ ~ a) ~ ~ ~ ~ V ~ C) C~ :~ O :~ {3 u~ ~ cn O c~ u~~- cn S O ~ C~ oo C) ~ ~ e -- ~= - 19

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TABLE 2 Minimal Dietary Energy Density Needed to Satisfy Energy Requirements According to Age and Number of Feedings Per Daya Number of Feedings Per Day 3 6- 9-11 12-23 24-36 Expec ted body weight, kgb 6.7 8.3 9.6 11.4 13.6 Usual energy requirement, kcal/dayC 770 915 1,010 1,175 1,360 Estimated gastric capacity, mid 200 250 290 340 410 Energy dens ity necessary to meet 8 48 46 44 43 41 energy requirement, 6 64 61 58 58 55 kcal/100 mle 4 96 92 87 86 83 aCalculated by subcommittee. b50th percentile of National Center for Health Statistics reference weights .16 CProduct of expected body weight and FAo/WH014 energy requirements of 115, 110, 105, 103, and 100 kcal/kg-day for ascending ale categories dEstimated as 3% of body weight, rounded to nearest 10 ml.2 e [ 100 ( energy requirement ) / ( feedings /day) ] / ( gas tric capac ity) . - 20

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adjuncts to fluid and electrolyte therapy, but never as a complete diet, because the concentrations of energy and nutrients in these preparations are usually too low. Digestibility can be influenced in various ways. Local food-processing techniques should be used whenever possible, because of their familiarity to the population. For example, the digestibility of legumes can be improved through familiar cooking, fermenting, or germinating techniques that are not ordinarily used for infant feeding; particle size can be reduced by using simple food mills. If it is desirable to reduce lactose content, partially fermented products, such as yogurt, can be used. Mixing dried-milk preparations with vegetables or cereals also reduces the lactose content of the final diet potentially without reducing the biologic value of the milk protein substantially. Because adequate food storage facilities are generally not available in the home, use of freshly prepared foods to minimize microbial contamination and growth should be encouraged. Reoffering of previously prepared food might be unavoidable, but reheating to a boil before feeding will reduce the hazards of consuming heavily contaminated food. Effective ways of communicating desirable food preparation practices need to be developed. For example, food preparation in a clinic or hospital can serve as an excellent educational tool for mothers*, and the opportunity should be taken whenever possible. Home visits by health care workers to reinforce food selection and food preparation lessons may well be essential for program success. FREQUENCY AND PROGRESSION OF FEEDING Breast-fed infants should continue to be nursed, even during Dehydration, by alternating between oral Dehydration solutions and breast milk. Recent studies *For convenience, "mother" is used to refer to the person with primary responsibility for the care of a child. - 21

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have shown that breast-feeding is an effective adjunct to ORT and offsets the need to provide plain water.20~22 Meals should be small and frequent in the early phase, because smaller meals are better tolerated. For older infants, at least six feedings a day should be attempted early in treatment; more frequent feedings are often necessary in younger infants. When children are hospitalized and refuse to eat, it is reasonable to consider continuous nasogastric feeding. This approach takes full advantage of residual digestive and absorptive capacities through the slow, steady introduction of small quantities of food. Nasogastric feeding might increase stool frequency without markedly increasing stool volume. The first meal by this route should consist of a 50% dilution of a 0.7-kcal/ml formulation; it should be followed in 3-4 hours by a meal that is diluted by 25% and then by a full-strength meal at the next feeding. Various strategies should be considered. For example, high volumes of dilute feedings might be tolerated better than equivalent amounts of nutrients in more concentrated feedings in early phases of treatment. When continuous nasogastric feeding is chosen, special care must be taken to ensure that the protocols for preparation and delivery include steps to minimize contamination. As in the preparation of other foods, it is best to prepare these immediately before use and not to leave more food than needed for 4 hours of feeding at room temperature at the bedside. During convalescence, defined as extending from cessation of liquid stools to return to preillness nutritional status, the quantity and frequency of feeding are determined by ad libitum intakes. Keeping track of a child's weight will ensure that ad libitum intakes meet the estimated nutrient needs and that the . . . . race or recovery is appropriates Flexibility in the reeking regimen promotes rapid convalescence. The early resumption of the customary feeding pattern, which probably includes three or four meals per day for older infants and very young children, is unlikely to provide sufficient nutrients for full recovery in a reasonable period. . 22

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MONITORING NUTRITIONAL THERAPY FOR DIARRHEA In the monitoring of nutritional therapy for diarrhea, close clinical observation of the child--including food intake, willingness to eat, activity, and apparent discomfort- might be more useful than merely keeping track of the frequency, quantity, and quality of stools. The mother plays a key role in the management of the dietary intake of a child with acute diarrhea, and her ability to assess the child's progress is therefore critical. To help gain the mother's confidence, health workers need to be sympathetic to her perception of the cause, course, and desired treatment for diarrhea. Many cultures distinguish a considerable array of diarrhea! illnesses, which have different causes and treatments. These can be the basis for deriving credible, simple, and physiologically sound guidelines to help a family manage diarrhea in the home, as well as to decide when a child should no longer be treated at home, but should be taken to a clinic or hospital. Easily recognized indicators of the severity of illness should be used in the formulation of these guidelines--e."., frequency of stools, duration of illness, clinical signs of dehydration, state of alertness, willingness to eat and drink, fever, and blood in the stools. Primary health care workers also need criteria for identifying infants who require more individualized attention. The criteria should reflect educational and physical resources available at each level of health care--home, and hospital. Sophisticated indicators of clinical (e.g., measurement of fluid input and stool output), but daily monitoring of weight gain is more feasible and highly useful. In an optimal regimen, a daily gain of at least 20 or 30 g in a previously healthy child can be expected. with much more status would be useful ~ . . clonic, , . weight gain seen in a recovering child who had been undernourished. Whenever care outside the home is warranted, health workers should involve the mother to the greatest extent possible. If she is taught basic facts about dehydration and feeding and participates in her child's care and recovery, she is more likely to recognize the importance of feeding during diarrhea and to continue feeding during future episodes. Ideally in all cases, - 23

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the mother should feed the child, for she usually has the experience necessary to succeed in this feeding. In many societies, however, women are overwhelmed with demands on their time, and finding the time necessary for the almost continuous feeding required for rapid recovery is difficult. If the time required for the optimal care of an acutely ill child is beyond the mother's resources, older siblings, grandparents, and fathers can often be enlisted to share the responsibility. Although following these guidelines will usually result in a successful outcome, dietary management sometimes fails. Failure cannot be predicted, but it is most likely in children who were already moderately to severely malnourished. In such children, salt and water deficits can be corrected, but hypokalemia, common in undernourished children, might persist for several days. Potassium-containing foods (e.g., citrus juices and bananas) are useful adjuncts to oral Dehydration. Whether at home or in the clinic, failure to respond can be anticipated if the patient's hydration status does not improve within 24 hours of the beginning of oral Dehydration and dietary management. Once feeding begins, refusal to eat, extensive vomiting after eating, and increased stool output are signs of food intolerance. complaints associated with the production of gas or explosive diarrhea are also important signs of food intolerance and are usually related to the carbohydrates being fed. High stool acidity and the presence of large amounts of reducing substances in the stool are due to malabsorption of carbohydrates. If clinical status is clearly worsening, the carbohydrates being fed should be changed or lessened. The presence of undigested food particles in the stool is evidence of the need for longer cooking time, greater use of refined raw materials, or the use of more finely pureed foods. Abdominal distention and In adjusting dietary management because of these adverse clinical responses, it is important to stress that it is the child, and not the stool, that is being treated. Feeding should continue even in children whose diarrhea! losses have continued, if their intake and weight gain are appropriate. Discontinuation of feeding should not be considered an option. If substantial - 24 -

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diarrhea continues, fluid replacement is necessary--with either oral rehydration solution or, when absolutely indicated, intravenous fluids--and the diet should not be changed too often. It usually takes 2-3 days to assess clinical response. This allows time for the natural diarrhea process to abate and any complications of feeding to become apparent. Continued feeding often improves absorptive capacity, as substrates needed for tissue repair are provided; however, treatment of more difficult cases might require the introduction of simpler, more easily digested foods. ANTIBIOTIC AND ANTIDIARRHEAL AGENTS Adequate fluid replacement alone can usually prevent death from secretory (watery) diarrhea. However, in some severe cases of secretory diarrhea (e.g., in cholera), adjunctive therapy with antibiotics markedly reduces the duration and volume of diarrhea. Antimicrobial therapy is more important for dysenteric diarrhea! illness than for secretory diarrhea. Antibiotics might decrease the duration of diarrhea, the period of discomfort, the potentially lethal complications of gram-negative bacterial infection, and the nutritional deterioration caused by excessive loss of protein in stools in such infection. Antidiarrheal drugs--such as diphenoxylate, loperamide, tincture of opium, and paregoric--can reduce symptoms of abdominal cramps, but do not substantially alter diarrhea! stool losses and might even prolong the illness. Adsorbents--such as kaolin, pectin, and activated charcoal--have no value in the treatment of infectious diarrhea. Bismuth subsalicylate in very large doses decreases the number of stools, but is not a practical or cost-effective therapeutic agent. In addition, substantial absorption of the salicylate might lead to toxicity, especially in children. Antisecretory drugs might reduce stool volume moderately, but are not effective enough to justify the expense and the risk of side effects. 25

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