Safety and Effectiveness of Homemade and Reconstituted Packet Cereal- based Oral Rehydration Solutions: A Randomized Clinical Trial

Alan Meyers, MD, MPH*; Amy Sampson, PhD*; Richard Saladino, MD‡; Sujata Dixit, PhD§; William Adams, MD*; and Alejandro Mondolfi, MD‡

ABSTRACT. Objectives. Parents may be deterred tended to take less ORS and total fluids. There were no from obtaining commercial oral rehydration solutions significant differences among the three groups in inci- (ORS) for their young children with acute diarrheal dis- dence of daily vomiting or stooling, duration of diarrhea, ease because of its availability and/or cost, especially if or weight gain. they are poor. We conducted a randomized clinical trial Conclusions. CBORS do not offer a clinically signif- to determine 1) whether low-income parents could safely icant advantage over glucose-based ORS. Homemade mix and administer cereal-based ORS (CBORS) both CBORS represent a treatment option in carefully selected from ingredients commonly found in the home and from cases, but it is not the safest alternative for regular clin- a premixed packet; 2) whether these CBORS were as ical use. Pediatrics 1997;100(5). URL: http://www. effective in maintaining hydration as commercial glu- pediatrics.org/cgi/content/full/100/5/e3; diarrhea, dehy- cose-based ORS; and 3) whether CBORS were more ef- dration, oral rehydration, cereal. fective in reducing severity and duration of illness. Methods. Children 4 to 36 months of age discharged from emergency departments and health centers with ABBREVIATIONS. ORT, oral rehydration therapy; ORS, oral re- acute diarrheal disease were randomized to receive either hydration solutions; CBORS, cereal-based oral rehydration solu- homemade CBORS, reconstituted packet CBORS, or Pe- tions; CI, confidence interval. dialyte. A study nurse saw the child at home each day until the illness resolved, and obtained capillary blood cute infectious diarrhea is a common illness for serum sodium at enrollment and at 24 to 48 hours; a in young children worldwide and in the sample of CBORS for sodium concentration; stool for United States, where children average be- pathogen analysis; and daily fluid intake, stool fre- A quency, and weight. tween 1.3 and 2.3 episodes per child per year for the 1 Results. A total of 232 children were enrolled, of first 5 years of life. Each year, approximately 1 of 5 whom 203 (88%) completed the study. Two parents (3%) children Ͻ5 years of age sees a physician for diar- in the homemade CBORS group and one parent (1%) in rhea, and 1.4% are hospitalized, resulting in the packet CBORS group made mixing errors resulting in Ͼ200 000 hospital admissions, or 10.6% of all admis- a high sodium concentration (>100 mEq/L); their chil- sions in this age group.1 It has been estimated that dren refused the solution and had normal serum sodium the annual national cost of hospitalization for rota- values. Mean CBORS sodium concentration for the re- virus-associated gastroenteritis was $352 million in mainder of the homemade CBORS group was 60 ؎ 10 1988.2 Some 300 children Ͻ5 years of age die in the -mEq/L, and for the packet CBORS group, 54 ؎ 13. Eigh teen children (11%) had abnormal serum sodium values United States each year because of diarrhea, a rate at presentation, which returned to normal in all groups in that has not declined since 1985. These deaths occur most cases. Three children (4.5%) in the homemade primarily in infants and disproportionately among CBORS group, 4 (6%) in the packet CBORS group, and 1 those who are African-American, premature, and liv- child (1.4%) in the Pedialyte group failed therapy. ing in Southern states and in metropolitan areas.3 Children refused to take homemade CBORS and Oral rehydration therapy (ORT) is safe, effective, packet CBORS (43% and 32%, respectively) more often less invasive, and less expensive than intravenous than Pedialyte (9%), and those in the CBORS groups rehydration for the treatment of diarrheal dehydra- tion, and its use in the home early in the course of From the *Division of General Pediatrics, Boston Medical Center, Boston illness can prevent the development of dehydra- University School of Medicine, Boston, Massachusetts; ‡Division of Emer- tion.4–8 ORT has been promoted in practice guide- gency Medicine, Children’s Hospital, Harvard Medical School, Boston, lines published by the American Academy of Pedi- Massachusetts; and §Department of Maternal and Child Health, Harvard 9,10 School of Public Health, Boston, Massachusetts. atrics (AAP) and the Centers for Disease Control This work was presented, in part, at the Ambulatory Pediatric Association and Prevention.11 However, there are economic bar- Annual Meeting, Washington, DC, May 9, 1996. riers to the use of ORT for low-income families,12 Dr Sampson is currently at the Perinatal Epidemiology Unit, Department of who may have to pay Ͼ$6 per liter in their neigh- Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT. borhood pharmacy for commercial oral rehydration Dr Dixit is currently at the Department of Human Nutrition and Dietetics, solutions (ORS). Coverage of commercial ORS varies University of Illinois at Chicago, Chicago, IL. among the state Medicaid programs,13 and one Received for publication Oct 29, 1996; accepted May 21, 1997. fourth of children in low-income families in the Reprint requests to (A.M.) Department of Pediatrics, Boston Medical Center, Boston, MA 02118. United States have no health insurance coverage at 14 PEDIATRICS (ISSN 0031 4005). Copyright © 1997 by the American Acad- all. emy of Pediatrics. A possible approach to this problem is the promo- http://www.pediatrics.org/cgi/content/full/100/5/Downloaded from www.aappublications.org/newse3 PEDIATRICS by guest on October Vol. 2, 100 2021 No. 5 November 1997 1of7 tion by health professionals of ORS prepared from consent, administered a structured questionnaire, and obtained ingredients commonly found in the home, as is done capillary blood for serum sodium assay. 15 Children were assigned to one of three treatment groups using in some programs in poor countries. However, randomization in blocks of nine subjects each. Group 1 received there are concerns that inaccurate measurement of homemade CBORS, prepared by mixing 2 cups of water, 1⁄2 cup of either sugar or salt could produce an ineffective or instant baby rice cereal (Gerber Products Co, Fremont, MI), and 1⁄4 dangerous mixture,16 and the safety and effective- level measuring teaspoon of table salt. This mixture was calcu- ness of homemade ORS in the United States has not lated to contain 50 mEq/L sodium, 1 mEq/L potassium, and 60 g/L cereal. Group 2 received CBORS, prepared by mixing ingre- been reported. Cereal-based oral rehydration solu- dients from a packet (provided by the Gerber Products Company) tions (CBORS) may be prepared from ingredients with 8 oz of water and containing 60 mEq/L sodium, 15 mEq/L found in most households, and homemade CBORS potassium, 48 mEq/L chloride, 25 mEq/L bicarbonate, and 80 should be safer than homemade sugar–salt solutions g/L cereal. Group 3 received Pedialyte (Abbott Laboratories, Columbus, OH), a commercially available glucose-based ORS (45 because of its lower osmolality if prepared with an mEq/L sodium, 20 mEq/L potassium, 35 mEq/L chloride, 30 17 inappropriately small volume of water. CBORS us- mEq/L citrate, and 25 g/L glucose). ing rice or other cereals at concentrations of 50 to 80 The study nurse assessed the ability of parents assigned to the g/L have been shown to be as effective as glucose- homemade and packet CBORS groups to correctly identify the based solutions in restoring and maintaining hydra- household measures used to prepare the solution. Parents were given all materials necessary to prepare and administer the study tion; in some studies, its use has reduced stool out- solution, including measuring utensils and containers for the put, shortened the course of diarrheal illness, CBORS groups and Pedialyte for the control group. Instructional reduced vomiting, decreased the volume of oral so- leaflets describing how to prepare and administer the study solu- lution needed, and improved weight gain.18,19 tions were given along with leaflets describing recommended feeding practice during diarrhea and prevention of transmission To assess the safety and effectiveness of home- of diarrheal disease. Parents were instructed to give the child made CBORS and CBORS prepared from a packet of her/his usual volume of liquids plus an additional volume, which premeasured dry ingredients, we conducted a ran- the nurse calculated as 10 mL/kg, for each diarrheal stool. They domized clinical trial. The hypotheses tested were 1) were advised to alternate the study solutions with the child’s other when adequately instructed, parents from a variety regular liquids, but to avoid sweetened beverages such as juice or soda pop unless diluted with an equal volume of plain water. It of ethnic and educational backgrounds are able to was suggested that liquids be given from a bottle or cup, but that safely prepare and administer CBORS made from if the child vomited the liquid, to give 1 teaspoonful every few ingredients commonly found in the home or recon- minutes until the vomiting ceased. To ensure uniformity of dietary stituted from a packet of premixed ingredients; 2) advice, parents were also advised to avoid milk and milk formula, but to continue the child’s usual solids. All educational materials CBORS prepared and administered at home are as were available in English, Spanish, and French. Parents also re- effective as commercially available glucose-based ceived diapers; soy formula;A&Dointment (Moore Medical, ORS in maintaining hydration in children with acute New Britain, CT); stickers, marker pens, and plastic bags for diarrheal disease; and 3) CBORS used in the mainte- labeling and collecting soiled diapers; and a canvas tote bag. nance phase of ORT are more effective than glucose- Parents were instructed to save all soiled diapers, mark each diaper with the time of its changing, and record fluid intake on a based ORS in decreasing the incidence of vomiting, daily log sheet. A study nurse visited the home each day, begin- number of stools per day, volume of ORS consumed, ning on the day after enrollment and continuing until the end of and duration of diarrhea, and in increasing weight illness, which was defined as passage of a formed stool followed gain. by at least 48 hours with no recurrence of diarrhea. At each visit, the study nurse reviewed the history of liquid intake and stool frequency, performed a clinical assessment of hydration status, METHODS and examined the soiled diapers collected since the previous visit. Children presenting to the pediatric emergency departments or On the first home visit, a sample of CBORS prepared by the parent primary care clinics of Boston City Hospital and Boston Children’s was collected and assayed for sodium, and stool was obtained for Hospital or any of seven Boston neighborhood health centers were pathogen analysis, which included culture for Salmonella, Shigella, considered eligible for study if they met the following criteria: 1) Yersinia, Campylobacter, and Escherichia coli O157:H7; specimens for age between 4 and 36 months; (2) discharged from treating site rotavirus antigen assay were frozen and assayed in batches (Sanofi with the diagnosis of acute diarrheal disease (defined as the pas- Diagnostics Pasteur, Chaska, MN). Within 24 to 48 hours after sage of at least one diarrheal stool in the 24 hours before registra- enrollment, a second capillary blood specimen was obtained for tion) with normal hydration status (in the judgment of the attend- serum sodium assay. A mixing failure was defined as CBORS ing physician) by the end of the visit; (3) had had rice introduced prepared by the parent with a sodium concentration of Ͼ100 to the diet; (4) had a legal guardian available who was fluent in mEq/L. In all such cases, a repeat test for serum sodium level was English, Spanish, French, or Haitian Creole, able to follow written obtained, CBORS discontinued, and the parent provided with instructions, available for home visits, and living within the geo- Pedialyte and followed until resolution of illness. If the child graphic range of the study; and (5) the attending physician agreed appeared to be dehydrated or had other signs of clinical concern, that the child may be included in the study. Children were con- the home visiting nurse referred the child back to her/his original sidered ineligible for study if they 1) presented with diarrhea of treatment or primary care site. A treatment failure was defined as Ͼ7 days’ duration; 2) had received antibiotics during the 7 days occurrence of dehydration as assessed by the child’s clinician at before presentation; 3) were known to have a chronic gastrointes- any time after enrollment or any child with serum sodium Ͼ150 tinal or immune disorder; or 4) if the study nurse judged the or Ͻ130 at 24 to 48 hours. These children were removed from the parent/guardian to be unable to adhere to the protocol instruc- study and given standard clinical care. A study nurse visited tions. Study nurses were on site at the two emergency depart- families at ϳ1 week after the end of illness to obtain an interval ments during peak visit times (usually 2 PM to 10 PM), 7 days per history and weight. Outcome measures included mixing and treat- week. They reviewed presenting complaints of all children in the ment failures, occurrence of vomiting, daily frequency and dura- target age range and approached the parent/guardian of those tion of diarrhea, and weight change at end of illness and 1 week patients whose presenting complaint was consistent with a diag- later. nosis of acute diarrheal disease (ie, diarrhea, vomiting, fever). Potentially eligible patients presenting at participating health cen- ters were identified by health center nursing staff, and a study Statistical Methods nurse was contacted to visit the health center and interview the Proportions were compared using the ␹2 statistic. Medians were parent. For study participants, the study nurse obtained informed examined when data distributions were skewed and compared

2of7 A CLINICAL TRIALDownloaded OF CEREAL-BASED from www.aappublications.org/news ORAL REHYDRATION by guest on October 2, 2021 using nonparametric median tests. The SPSS statistical package sentation, and 72% reported vomiting. In the judg- was used for statistical analysis.20 Exact one-sided upper limit of ment of the attending physician, 60% of children 95% confidence intervals (CI) was calculated for mixing failure rates and treatment failure rates using the Fisher exact confidence were not dehydrated, whereas 34% had mild, 5% limits, as described by Sahai and Khurshid.21 In comparing total moderate, and 0.5% severe dehydration. Stool sam- liquid intake data among the three groups, data were edited to ples were available for rotavirus assay from 175 chil- remove biologically implausible outliers (total fluid intake Ͼ300 dren (86%), of whom 47 (27%) had a positive result. mL/kg/day). A total of 163 specimens (80%) were assayed for RESULTS bacterial pathogens, of which 5 (3%) were positive for Salmonella and 3 (2%) for Campylobacter. Demo- Between November 1, 1994 and April 28, 1996, 505 graphics, illness characteristics, etiology, and degree parents whose children appeared to meet the study of dehydration did not vary significantly by treat- criteria were invited to participate in the study, of ment group assignment. whom 177 (35%) declined and 96 (19%) were found When asked whether they had heard of drinks to be ineligible on further examination. A total of 232 that could be purchased in a store or pharmacy to children were enrolled, of whom 203 (88%) were treat children with diarrhea and/or vomiting, 157 followed to an endpoint (end of illness or mixing/ parents (77%) responded that they had, with 151 treatment failure). Children lost to follow-up (n ϭ 29) (96%) naming Pedialyte. A total of 121 parents and those followed to an endpoint did not differ by (60%) reported that they had given their child demographics, illness history, stool pathogens, or Pedialyte in the past, and 70 children (36%) were treatment group. Data are presented for the 203 chil- being given Pedialyte at the time of enrollment. dren followed to an endpoint. Demographics of the There was no difference in history of previous ORS children are shown in Table 1: mean age was 15 Ϯ 8 use by treatment group (P ϭ .31). A total of 67% of months; 38% were Latino (a category which included parents reported that they had a measuring cup in Puerto Rican [18%], Central American [10%], Domin- the household, 50% had a measuring spoon set, ican [6%], and other Latino [4%]), 30% were African- 97% had salt, 95% had sugar, and 60% had instant American, and 10% were Haitian; 87% of children baby rice cereal; 26% had all of the ingredients participated in the Special Supplemental Food Pro- necessary to prepare homemade CBORS. gram for Women, Infants, and Children. Sixty-five percent of mothers reported ever breastfeeding. Ninety-seven percent of parents reported the child’s CBORS Sodium Concentration having a primary care clinician, and 56% had not The distribution of sodium values in the homemade contacted their doctor before bringing the child for solutions prepared by study parents is shown in Figure care. 1. There were two mixing failures in this group (2/66 ϭ Illness characteristics are shown in Table 2. Parents 3.0% [one-sided upper limit of 95% CI ϭ 9.2%]). In the reported a mean of 6.6 stools in the 24 hours before first case, the mother mixed a solution with a sodium presentation and 2.2 days with diarrhea before pre- concentration of 255; she reported that she had not read

TABLE 1. Sample Demographics (N, %) Total Group 1 Group 2 Group 3 P N ϭ 203 (Homemade) (Packet) (Pedialyte) n ϭ 66 n ϭ 68 n ϭ 69 Age, months; mean Ϯ SD 15.3 Ϯ 8.2 16.5 Ϯ 7.9 13.7 Ϯ 7.7 15.8 Ϯ 8.8 0.12 Sex male 115 (57) 38 (58) 38 (56) 39 (57) 0.98 female 88 (43) 28 (42) 30 (44) 30 (43) Ethnicity Latino 75 (38) 25 (40) 24 (36) 26 (39) African-American 60 (30) 16 (25) 21 (31) 23 (34) 0.73 Haitian 19 (10) 9 (14) 6 (9) 4 (6) Other 43 (22) 13 (21) 16 (24) 14 (21) Maternal age, years; mean Ϯ SD 25.6 Ϯ 6.3 26.5 Ϯ 5.9 24.7 Ϯ 5.8 25.6 Ϯ 7.0 0.25 Maternal education Less than high school 77 (41) 23 (38) 27 (44) 27 (41) High school graduate 70 (37) 19 (32) 24 (39) 27 (41) 0.38 Beyond high school 40 (21) 18 (30) 10 (16) 12 (18) Health insurance Medicaid 121 (63) 34 (56) 43 (67) 44 (66) HMO* 26 (13) 8 (13) 8 (13) 10 (15) 0.61 None 35 (18) 16 (26) 10 (16) 9 (13) Private 7 (4) 3 (5) 2 (3) 2 (3) Other 3 (2) 0 1 (2) 2 (3) WIC participation 168 (87) 56 (87) 55 (86) 57 (86) 0.96 AFDC participation 92 (48) 28 (44) 28 (44) 36 (55) 0.31 Food stamp participation 94 (49) 30 (46) 28 (44) 36 (55) 0.37 Child in day care 27 (14) 06 (9) 11 (17) 10 (15) 0.61 Household has telephone 173 (88) 58 (89) 55 (86) 60 (88) 0.84 Missing values not included. Percentages may not add up to 100% because of rounding. * An undetermined number of patients enrolled in HMOs were also Medicaid recipients.

Downloaded from www.aappublications.org/newshttp://www.pediatrics.org/cgi/content/full/100/5/ by guest on October 2, 2021 e3 3of7 TABLE 2. Illness Characteristics Total Group 1 Group 2 Group 3 P N ϭ 203 (Homemade) (Packet) (Pedialyte) n ϭ 66 n ϭ 68 n ϭ 69 Duration of diarrhea before presentation, 2.2 (1.8) 2.1 (1.7) 2.4 (1.8) 2.2 (1.9) 0.69 days, mean, SD Frequency of diarrhea in 24 hr before 6.6 (5.3) 6.6 (5.6) 7.3 (4.0) 5.9 (6.0) 0.32 presentation, mean, SD History of vomiting, N (%) 144 (72) 50 (78) 44 (65) 51 (74) 0.21 History of fever, N (%) 118 (60) 37 (60) 43 (64) 38 (57) 0.67 History of diarrhea, N (%) 110 (56) 37 (59) 34 (51) 39 (57) 0.70 Previous physician’s estimate of degree of dehydration, N (%) None 166 (60) 34 (55) 43 (66) 39 (59) Mild 66 (34) 23 (37) 19 (29) 24 (36) 0.66 Moderate 10 (4) 4 (6) 3 (5) 3 (5) Severe 1 (5) 1 (2) 0 0 Rehydrated intravenously, N (%) 18 (9) 9 (14) 3 (4) 6 (9) 0.17 Stool pathogens, N (%) Rotavirus 47 (27) 17 (29) 15 (25) 15 (27) 0.90 Salmonella 5 (3) 3 (5) 1 (2) 1 (2) 0.47 Campylobacter 3 (2) 2 (4) 0 1 (2) 0.38 the directions when preparing the study mixture, nor dium values were normal. None of these children did she remember which spoon she had used to mea- failed treatment. sure the salt. When asked by the study nurse to prepare The distribution of sodium concentrations in the the solution again, the mother replied that she had premixed packet group is shown in Figure 2. There given away both the instructions and measuring mate- was one mixing failure in this group (1/68 ϭ 1.5% rials. In the second case, the father had received the [one-sided upper limit of 95% CI ϭ 6.8%]). The enrollment instructions, but the mother had prepared mother reported that the child’s father had added the solution; the mixture sample had a sodium concen- salt to the mixture to improve its taste because the tration of 191 mEq/L. Both children were reported to child was refusing to drink it. The solution sample have refused the solution, and both were found to have had a sodium concentration of 138 mEq/L, the normal serum sodium values. The mean solution so- child was reported to have refused the solution, dium concentration for the remainder of the group was and his follow-up serum sodium value was nor- 54 Ϯ 13 mEq/L. Five parents mixed solutions with low mal. One other parent reported adding sugar to the sodium concentration (ranging from 10 to 37 mEq/L). mixture to improve its taste. The mean solution In one case, the initial serum sodium concentration was sodium concentration for the remainder of the 148 mEq/L, and follow-up was 140 mEq/L after ad- group was 60 Ϯ 10 mEq/L. Two parents mixed ministration of a solution with 32 mEq/L sodium. In solutions with low sodium concentration (both the other four cases, initial and follow-up serum so- were 23); in both cases, initial and follow-up serum

Fig 1. Homemade cereal-based ORS sodium concentration. Fig 2. Packet cereal-based ORS sodium concentration.

4of7 A CLINICAL TRIALDownloaded OF CEREAL-BASED from www.aappublications.org/news ORAL REHYDRATION by guest on October 2, 2021 sodium values were normal. Neither of these chil- of the children in the homemade cereal ORS group dren failed treatment. did not take any of the assigned solution, compared with 32% of those in the packet group and 9% of Serum Sodium Concentration those in the Pedialyte group (homemade vs packet, Mean serum sodium concentration was 139 Ϯ 3.0 P ϭ .3; homemade vs Pedialyte, P ϭ .00003; packet vs mEq/L at enrollment and 139 Ϯ 2.5 mEq/L at 24 to Pedialyte, P ϭ .003). This pattern remained consis- 48 hours’ follow-up, and did not differ significantly tent on most of the following 5 days of illness. Chil- by treatment group. Considering all children with dren who took none of the cereal-based solutions in enrollment and follow-up serum sodium determina- the first 24 hours were not more likely to have been tions (N ϭ 169), 18 patients (11%) had abnormal on Pedialyte at enrollment nor to have had previous serum sodium values at enrollment. In all of these experience with Pedialyte. A total of 21% of parents cases, serum sodium was determined for study pur- of children taking none of the cereal-based solutions poses and not because it was considered indicated by reported that they had not offered the child the study the examining physician. Their follow-up sodium solution. Among children who did not refuse ORS, values returned to normal in 89% of cases (Fig 3). those in the homemade CBORS group consumed less Two children with abnormal enrollment values and ORS than those in the Pedialyte group on days 2 and three children with normal enrollment values had a 4 (Table 3). Among all children, those in the home- follow-up serum sodium value that was abnormal, made CBORS group consumed less total fluid than but none were in the range defined as treatment those in the Pedialyte group on days 2 and 3, and less failure and all were clinically healthy at follow-up. than those in the packet group on day 2 (Table 4). No child with an abnormal serum sodium value on At the end of the child’s illness, parents were reevaluation required hospitalization. asked their opinion of the assigned solution. There were no significant differences among the three Treatment Failures groups in the proportion of parents who found the Among children in the homemade CBORS group, smell or consistency of the solution to be unpleasant there were three treatment failures (4.5%, [one-sided (8% to 13%), although more parents found the color upper limit of 95% CI ϭ 11.3%]); two children were of the homemade (9%) and the packet (15%) CBORS hospitalized. There were four treatment failures in to be unpleasant compared with those assigned Pe- the premixed packet CBORS group (6% [one-sided dialyte (0%) (P ϭ .0005). Perception of unpleasant upper limit of 95% CI ϭ 13%]); two were hospital- qualities was not associated with the child’s not tak- ized. One child failed treatment in the Pedialyte ing the assigned solution, nor was the parents’ per- group (1.4% [one-sided upper limit of 95% CI ϭ ception that the CBORS was too thick to serve 6.7%]) and was hospitalized. These proportions are (homemade 16%, packet 7%). not significantly different (P ϭ .39).

Oral Liquid Intake Vomiting, Stool Frequency, Duration of Illness, and Most parents did not maintain complete written Weight Gain records of oral intake as requested, thus, daily recall There were no differences by treatment group as- was relied on to estimate quantitative liquid con- signment in the proportion of children vomiting per sumption. In the first 24 hours after enrollment, 43% day for the first 7 days of illness after enrollment,

Fig 3. Abnormal serum sodium at en- rollment (time 1) and at 24 to 48 hours (time 2).

Downloaded from www.aappublications.org/newshttp://www.pediatrics.org/cgi/content/full/100/5/ by guest on October 2, 2021 e3 5of7 TABLE 3. ORS Intake by Treatment Group (Median mL/kg/d)* Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Homemade CBORS 19 24† 31 26† 25 12 22 Packet CBORS 22 31 29 37 21 37 65 Pedialyte 21 36† 34 51† 22 52 34 * Excludes children taking none of the assigned solutions on day 1. † .01 Ͻ P Ͻ .05.

TABLE 4. Total Fluid Intake by Treatment Group (Median mL/kg/d) Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Homemade CBORS 45* 60† 66† 72 95 84 106 Packet CBORS 58 87† 85 69 84 86 97 Pedialyte 56* 89† 89† 94 83 110 101 * .05 Ͻ P Ͻ .1. † .01 Ͻ P Ͻ .05. which ranged from 17% to 28% on day 1 and de- countries, where wide ranges of accuracy in solution clined thereafter, nor in median number of diarrheal sodium concentration have been found.18,22–24 Few stools, which ranged from 1 to 2. There were seven such studies have been reported from industrialized cases of diarrhea persisting Ͼ14 days beyond enroll- countries; studies from Italy25 and England26 have ment: three in the homemade group, and two each in shown a high variability of homemade sugar–salt the packet and Pedialyte groups. In all these cases, ORS. The greater accuracy of the parents in our illness resolved in the third week after enrollment. study may be attributable to the fact that they had These cases were excluded from analysis of duration been instructed personally in solution preparation by of illness. Median duration of diarrheal illness did a nurse in addition to having received written in- not differ by treatment group: for children in the structions. homemade CBORS group, median duration (range) Children were less likely to take the cereal-based was 111 hours (7 to 335); for those in the packet than the glucose-based solution. Median ORS and CBORS group, 97 hours (19 to 327); and for those in total fluid consumption reported by parents were the Pedialyte group, 92 hours (10 to 310). low for all three study groups; this might reflect Using 80% power with ␣ ϭ 0.05, and given the inaccurate reporting, because most parents did not sample sizes and SDs observed, we calculated that adhere to instructions to keep a written record of the smallest detectable difference between group 1 fluid intake. Nonetheless, treatment failure rates and group 3 was 38 hours, and between group 2 and were similarly low for the three treatment groups group 3, 39 hours. To assess potential therapeutic and within the range of failure rates reported in other differences among the children with the most severe trials of outpatient ORT in the United States.27–32 The disease, we repeated this analysis using only the three solutions studied were found to be equally children in the upper tercile of ORS consumption in effective in maintaining hydration and correcting the first 24 hours and, again, found no significant both hypernatremia and hyponatremia. We did not differences in proportion of children vomiting, stool find any advantage in treatment outcome among frequency, or duration of diarrhea. We obtained the children in the CBORS groups compared with those same results when we restricted the analysis to those assigned glucose-based ORS. This may have been in the upper tercile of stool frequency on day 1, and attributable to the relative mildness of illness in the again when we restricted analysis to those children children studied. Furthermore, a recent metaanalysis who were judged to be dehydrated at presentation. has shown no significant reduction in stool output in Between enrollment and end of illness, children children with acute, noncholera diarrhea given rice- gained a median of 0.180 kg (range, Ϫ0.125 to 1.83 based ORS.33,34 Thus, efforts to prevent the morbidity kg), or 1.8% of enrollment (hydrated) weight, and and mortality of acute diarrheal disease in US chil- between end of illness and 1 week follow-up, 0.200 dren should not be focused primarily on the use of kg (range, Ϫ0.55 to 1.54), or 2.0%. There were no cereal-based as opposed to glucose-based ORS. differences in weight change among treatment Whether using an ORS at the onset of illness is groups. more effective in preventing dehydration than sim- ply increasing the child’s usual fluids is not known; DISCUSSION the AAP practice parameter10 states that ORS is not Most parents in this low-income and multiethnic necessary for the child without dehydration, sample were able to safely prepare CBORS both from whereas the Centers for Disease Control and Preven- ingredients commonly found in the home and from a tion recommends that “families with infants and premixed packet (97% and 99%, respectively). How- small children should be encouraged to keep a sup- ever, several potentially hazardous mixing errors ply of ORS at home at all times and use the solution were made, although in none of these cases was there when diarrhea first occurs in the child.”11 There are an adverse clinical outcome. Most other reports of no data available to answer this question. It is our trials of homemade ORS preparation are from poor clinical impression that the majority of children with

6of7 A CLINICAL TRIALDownloaded OF CEREAL-BASED from www.aappublications.org/news ORAL REHYDRATION by guest on October 2, 2021 acute gastroenteritis will do well even without ORS, 5. Klish WJ. Use of oral fluids in treatment of diarrhea. Pediatr Rev. but there are a minority of children who develop 1985;7:27–30 6. Santosham M, Brown KH, Sack RB. Oral rehydration therapy and dietary severe purging, especially with rotavirus infection, therapy for acute childhood diarrhea. Pediatr Rev. 1987;8:273–278 and it is these children who will be most in need of 7. Goepp JG, Katz SA. Oral rehydration therapy. Am Fam Physician. 1993; an appropriate ORS to maintain hydration and 47:843–851 prevent hyponatremia and hypernatremia. Our 8. Richards L, Claeson M, Pierce NF. Management of acute diarrhea in data show that homemade CBORS is not the safest children: lessons learned. Pediatr Infect Dis J. 1993;12:5–9 9. American Academy of Pediatrics, Committee on Nutrition. Use of oral alternative, because it carries the risk of potentially fluid therapy and posttreatment feeding following enteritis in children dangerous mixing errors even with the most care- in a developed country. Pediatrics. 1985;75:358–361 ful supervision, and it is likely that the children 10. American Academy of Pediatrics, Provisional Committee on Quality most severely affected with dehydrating diarrhea Improvement, Subcommittee on Acute Gastroenteritis. Practice would be most likely to consume, if offered, a parameter: the management of acute gastroenteritis young children. Pediatrics. 1996;97:424–436 mixture erroneously prepared with too much salt. 11. Centers for Disease Control and Prevention. The management of acute There are circumstances in which homemade diarrhea in children: oral rehydration, maintenance, and nutritional CBORS may be considered an option, eg, in the therapy. MMWR. 1992;41:1–20 case of a young child with rapid purging whose 12. Meyers A, Siegel B, Vinci R. Economic barriers to the use of oral family is unable to obtain commercial ORS and is rehydration therapy: a case report. JAMA. 1991;265:1724–1725 13. Cohen MB, Hardin J. Medicaid coverage of oral rehydration solutions. in telephone contact with a clinician who has con- N Engl J Med. 1993;329:211. Letter fidence in their ability to prepare the solution cor- 14. US General Accounting Office. Health Insurance for Children: Private rectly. Insurance Coverage Continues to Deteriorate. Washington, DC: GAO/ The packet-reconstituted CBORS was diluted cor- HEHS-96-129; 1996. US GAO rectly in all cases, although errors in preparation can 15. Werner D. Beyond pediatrics: the health and survival of disadvantaged children. E. H. Christopherson lectureship on international child health. still be made, especially by the addition of extra Pediatrics. 1993;91:703–705 ingredients to the ORS (as occurred in two cases in 16. Snyder JD, Molla M, Cash RA. Home-based therapy for diarrhea. J Pe- our study), which can also occur with a premixed diatr Gastroenterol Nutr. 1990;11:438–447 commercial solution such as Pedialyte. A premixed 17. Greenough WB III, Khin-Maung-U. Cereal-based oral rehydration ther- packet for reconstitution with water may represent apy. II. Strategic issues for its implementation in national diarrheal disease control programs. J Pediatr. 1991;118:S80–S85 the most practical way to ensure that families at 18. Khin-Maung-U, Greenough WB III. Cereal-based oral rehydration ther- highest risk have ORS on hand when the need arises. apy. I. Clinical studies. J Pediatr. 1991;118:S72–S79 Such packets could be distributed readily at primary 19. Gore SM, Fontaine O, Pierce NF. Impact of rice based oral rehydration care facilities, although the cost might need to be solution on stool output and duration of diarrhoea: meta-analysis of 13 subsidized to remove the economic barrier standing clinical trials. Br Med J 1992;304:287–291 a 20. SPSS User’s Guide. 3rd ed. Chicago, IL: SPSS, Inc; 1988 between poor families and ORT. 21. Sahai H, Khurshid A. Statistics in Epidemiology. New York: CRC Press; 1995:173 ACKNOWLEDGMENTS 22. Kassaye M, Larson C, Carlson D. A randomized community trial of This study was funded jointly by the Agency for Health Care prepackaged and homemade oral rehydration therapies. Arch Pediatr Policy and Research and the Child Health Foundation (Columbia, Adolesc Med. 1994;148:1288–1292 MD) Grant R01 HS08335-01. 23. Islam MA, Biswas E, Rahman AK, Chakma DB. Factors associated with We thank the nursing and medical staffs of Boston City Hos- safe preparation and home use of sugar–salt solution. Public Health. pital, Boston Children’s Hospital, Codman Square Neighborhood 1994;108:55–59 Health Center, Whittier Street Neighborhood Health Center, Up- 24. Ekanem EE, Akitoye CO, Adedeji OT, Salako QA. A quantitative as- ham’s Corner Health Center, Dimock Street Neighborhood Health sessment of the Nigerian mother’s ability to prepare salt–sugar solution Center, Martha Elliott Health Center, South End Neighborhood for the home management of diarrhea. J Royal Soc Health. 1993;113: Health Center, and Mattapan Health Center for their collaboration 243–246 and support. We also thank the study nurses—Marie Graham, 25. Fontana M, Zuin G, Paccagnini S, et al. Home-made oral rehydration Jacqueline LaGuerre, Mary Lenihan, Robert Marrero, Ann-Marie solutions: variations in composition. Acta Paediatr Scand. 1991;80: McCarthy, Gertrude Monestime, and Caridad Ramirez—for their 720–722 excellent nursing care and diligent attention; Dr Ronald Kleinman 26. Hutching P, Wilson C, Manly JAE, Walker-Smith JA. Oral solutions for for his review of the study design and monitoring of safety data; infantile gastroenteritis—variations in composition. Arch Dis Child. and Dr Adrienne Cupples, Suzette Levinson, and Dr Robert 1980;55:616–618 Houser for statistical advice and calculations. 27. Gavin N, Merrick N, Davidson B. Efficacy of glucose-based oral rehy- dration therapy. Pediatrics. 1996;98:45–51 REFERENCES 28. Listernick R, Zieserl E, Davis AT. Oral glucose-electrolyte solutions as maintenance therapy of acute diarrhea. Am J Dis Child. 1985;139:571–574 1. Glass RI, Lew JF, Gangarosa RE, et al. Estimates of morbidity and 29. Santosham M, Goepp J, Burns B, et al. Role of a soy-based lactose-free mortality rates for diarrheal diseases in American children. J Pediatr. formula in the outpatient management of diarrhea. Pediatrics. 1991;87: 1991;118:S27–S33 619–622 2. Matson DO, Estes MK. Impact of rotavirus infection at a large pediatric 30. Santosham M, Burns B, Nadkarni V, et al. Oral rehydration therapy for hospital. J Infect Dis. 1990;162:598–604 3. Kilgore PE, Holman RC, Clarke MJ, Glass RI. Trends of diarrheal acute diarrhea in ambulatory children in the United States: a double- disease- associated mortality in US children, 1968 through 1991. JAMA. blind comparison of four different solutions. Pediatrics. 1985;76:159–166 1995;274:1143–1148 31. Herzog LW, Bithoney WG, Grand RJ. High sodium rehydration solutions 4. Santosham M, Greenough WB III. Oral rehydration therapy: a global in well-nourished outpatients. Acta Paediatr Scand. 1987;76:306–310 perspective. J Pediatr. 1991;118:S44–S51 32. Leung AKC, Taylor PG, Geoffroy L, Darling P. Efficacy and safety of two oral solutions as maintenance therapy for acute diarrhea: a double- blind, randomized, multicenter trial. Clin Pediatr. 1988;27:359–364 a Glucose-based ORS packets may be obtained from Pharmacia & Upjohn, 33. Bhan MK, Mahalanabis D, Fontaine O, Pierce NF. Clinical trials of Kalamzoo, MI 49001 (KaoLectrolyte) and Jianas Brothers Packaging Co, improved oral rehydration formulations: a review. 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Downloaded from www.aappublications.org/news by guest on October 2, 2021 Safety and Effectiveness of Homemade and Reconstituted Packet Cereal-based Oral Rehydration Solutions: A Randomized Clinical Trial Alan Meyers, Amy Sampson, Richard Saladino, Sujata Dixit, William Adams and Alejandro Mondolfi Pediatrics 1997;100;e3 DOI: 10.1542/peds.100.5.e3

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