The World Health Organization Oral Rehydration Solution in US Pediatric Practice: Title and subTitle BreakA Randomized Trial to Evaluate Parent Satisfaction FREE

ACUTE gastroenteritis is a common and costly occurrence among US children. Each year, children younger than 5 years average 1.3 to 2.7 episodes of diarrhea each, resulting in 3 million pediatric office visits, 200,000 hospitalizations, and 300 potentially preventable deaths.^{1 - 2} The annual cost of care for these children in the outpatient setting alone is more than $1 billion.³

Appropriate oral rehydration solutions (ORSs) are the mainstay of treatment for acute gastroenteritis. These electrolyte solutions can be used for rehydration as well as maintenance, and can prevent most diarrhea-related complications. Yet ORSs are grossly underused for a variety of reasons, including cost.^{4 - 11} One liter of commercially prepared oral rehydration solution (C-ORS) is recommended for use only 48 hours once opened. A survey of Baltimore (Md) and Cincinnati (Ohio) pharmacies, supermarkets, and convenience stores revealed a range of costs, from $3 to $4.50 for generic products and $5 to $6.50 for name-brand solutions. Few Medicaid and commercial insurance plans provide for these solutions on their formularies.^{11 - 13}

The World Health Organization ORS (WHO-ORS), used extensively in developing countries, is inexpensive and efficacious. Measured solutes are dispensed in a packet to be mixed with 1 L of tap water. The WHO-ORS packets are available in the United States at a cost of $0.55 per liter and carry American Academy of Pediatrics (AAP) approval.^{4 ,14}

Despite a higher sodium content (90 mmol/L) than solutions commercially prepared in the US (45 mmol/L) (Table 1), the WHO solution will correct electrolyte imbalances, including hyponatremia and hypernatremia.^{15 - 17} Extensive studies reveal that this WHO-ORS can be used safely and effectively to treat US children with gastroenteritis of all origins.^{16 ,18} Recent multicenter studies have compared a lower-osmolality WHO-ORS with the standard solution. These trials demonstrate equal safety and efficacy, but reduced stool output and vomiting among subjects receiving the lower-osmolality solution.^{19 - 21}

Despite the availability of WHO-ORS from US manufacturers, US practitioners rarely recommend it.^{5 ,22} This may be because of their limited experience with the solution and concerns that parents will not accept or administer it. This study was conducted to determine caretaker acceptance of a packet-based solution that requires preparation vs a C-ORS.

We conducted a randomized controlled trial in an urban pediatric clinic (Harriet Lane Clinic, Johns Hopkins Children's Center) and a suburban family medicine clinic (Franklin Square Family Health Center) in Baltimore.

Children aged 3 to 47 months presenting with diarrhea to these clinics between November 1996 and August 1997 were eligible if they had 7 or fewer days of diarrhea, were suitable for outpatient treatment, and had 5% or less dehydration by clinical assessment. Diarrhea was defined as 3 or more loose or watery stools per day. Children who were fed exclusively by gastrostomy tube were excluded. Recruitment occurred during daytime and evening session hours, from 9 AM until 10 PM. Study protocol and consent procedures were approved by the Institutional Review Boards of the Johns Hopkins Hospitals and Franklin Square Hospital Center. Written informed consent was obtained from the caretaker of each participant.

Once evaluated by a practitioner and deemed eligible, patients were referred to a research assistant for possible enrollment. After informed consent was obtained, a structured enrollment interview was conducted to obtain information regarding the current illness and patient demographics. Children were then assigned to 1 of 2 groups using randomization in blocks of 8 subjects each. Group A families received a C-ORS (Pedialyte; Ross Nutritionals, Columbus, Ohio). Group B families were given sachets of a lower-sodium WHO-ORS (74 mmol/L) and a 1 L container for preparation. The resulting solutions differed slightly in electrolyte composition, but were similar with respect to osmolality (Table 1). Mixing instructions for the packet-based solution were provided in writing and orally. For both groups, solutions were provided free of charge and were to be offered along with breast milk, formula, and starchy food, in accordance with AAP recommendations.¹⁴ Families were allowed to add certain flavorings to either solution (unsweetened Kool-Aid [Kraft Foods Inc, Northfield, Ill] Crystal-Light [Kraft Foods Inc, Northfield, Ill], or juice just to "color" the solution). These additions do not significantly alter the electrolyte composition and osmolality.²³ Detailed illness treatment, including amount and frequency of ORS administration, were left to the practitioner and provided to families before study enrollment. Study participation determined only which ORS would be offered to the child. Caretakers were asked to offer the assigned solution for 48 hours.

During the enrollment interview, caretakers were shown each solution, and data were obtained regarding their willingness to pay. Caretakers provided the initial and maximum dollar amounts, to the nearest $0.50, that they would pay for each solution if they purchased it in a retail store.

On the second day of solution use, a trained research assistant administered a telephone follow-up questionnaire. The interview contained items to assess status of the child's illness and caretaker use of and satisfaction with the assigned solution. During the interview, families were told the approximate retail cost of each solution, $5 for the C-ORS and $0.55 for the WHO-ORS.

As we could find no existing tool to measure caretaker satisfaction with a treatment regimen, we developed our own. Our instrument was modeled after the Parent Satisfaction Questionnaire, a reliable and valid tool used to assess parent satisfaction with a medical encounter.²⁴ Test-retest evaluation of our instrument yielded a Pearson correlation coefficient of r=0.84. The instrument elicited caretaker satisfaction ratings on several aspects of the solutions. Satisfaction with preparation time, ease in getting the child to drink, appearance, effectiveness, cost, and willingness to purchase in the future and to recommend to friends/relatives were assessed. Finally, caretakers were asked to rate their overall satisfaction with the assigned solution. Satisfaction with each aspect was measured on a 5-point Likert type scale (1, very dissatisfied to 5, very satisfied).

We sought to show that the WHO-ORS was received by caretakers with a level of satisfaction at least equal to that of the accepted treatment, C-ORS. Thus, we used a test of equivalence to estimate sample size.²⁵ We defined a difference of less than 15% overall satisfaction between the groups as indicative of equivalence (ϵ). For an α=.10 (1-sided) and power of 0.80, with π₁=π₂=80% satisfied/very satisfied with their assigned solution, the number of subjects required in each group was 65.

The significance of differences in outcomes between the groups was tested using χ², Mann-Whitney U, and t tests for nominal, ordinal, and interval measures, respectively.

Of 97 families enrolled, 91 completed the follow-up interview. One caretaker decided not to offer her child any solution, and the remaining 5 families were lost to follow-up. Measured baseline characteristics of these families were not different than those completing the study.

Mean±SD ages at enrollment were 19.0±12.0 months for children and 25.6±7.0 years for caretakers and were similar between the groups. The enrolled caretaker was the child's mother for 92 dyads. Other caretakers included 3 grandmothers, 1 foster mother, and 1 father. The groups did not differ significantly with respect to measured demographic factors at baseline (Table 2).

The groups were similar in terms of most baseline illness characteristics (Table 2), including duration of diarrhea before study enrollment and the caretaker's primary concern prompting the visit. However, slightly more families in the C-ORS group had used Pedialyte for the current illness before study enrollment (P=.06).

For C-ORS, caretakers would pay a maximum price ranging from $2 to $15, with a median of $5. For WHO-ORS, maximum prices ranged from $0.50 to $15, with a median of $4. Amounts caretakers were willing to pay for either solution did not affect overall satisfaction with their assigned solution (P=.60 and P=.27 for C-ORS and WHO-ORS, respectively, using χ² test).

Of the 91 families completing the study, 52 opened 1, 31 opened 2, 7 opened 3, and 1 opened 4 packets or bottles during the 48-hour study period. Significantly more solution was used by families receiving WHO-ORS (P=.03) (Table 3). Of families receiving C-ORS, 17 (40%) added a flavoring; 24 (49%) of WHO-ORS families did so (P=.40).

At the time of the follow-up interview, occurring 48 to 60 hours after study enrollment, 17 children (33%) in the C-ORS group and 23 children (47%) in the WHO-ORS group still had diarrhea (P=.20). No adverse effects attributable to either study solution were reported in the interviews. No child in either group required subsequent inpatient management for dehydration or other complications of acute gastroenteritis.

When caretaker perceptions of individual attributes of the solutions were examined, no differences in satisfaction were found with preparation time, ease of administration, appearance, or effectiveness. Families of children in the WHO-ORS group had a higher willingness to purchase in the future and to recommend to friends. They also had higher satisfaction with cost and greater overall satisfaction (Table 4) (Figure 1 and Figure 2). These differences remained significant after controlling for prior use of the C-ORS, Pedialyte.

Significantly more families using the WHO-ORS rated their overall satisfaction as "very satisfied" than did families using C-ORS (P=.001) (Table 5). This score was not associated with any of the demographic or baseline illness characteristics outlined in Table 2 (P≥.20, for all) or by persistence of diarrhea at follow-up interview (P=.40). There was no significant relationship between the number of packets/bottles opened and overall satisfaction.

Each year, between 21 and 37 million episodes of diarrhea are experienced by US children younger than 5 years.¹ As recommended by the AAP and others, children with mild diarrhea and no dehydration require only continuation of a regular diet and increased fluid intake.^{14 ,26} However, when any element of dehydration is present, early and proper administration of ORS can prevent the need for hospitalization and intravenous therapy in more than 90% of cases.²⁷ Indeed, many practitioners routinely instruct parents of children with acute diarrhea to give an ORS in hopes of preventing dehydration. Thus, access to an ORS is desirable for all children.

The cost of commonly available premixed solutions presents a barrier for many families. These solutions are rarely covered by commercial or Medicaid insurance plans.^{11 - 13} Lack of access results in preventable emergency department visits, hospitalizations, and has even been implicated in the death of an infant whose mother could not afford the Pedialyte recommended by her child's practitioner.^{7 ,11}

Lower-cost alternatives to commercially prepared ORS include homemade and packet-based solutions. Using water, sugar, salt, and, optionally, infant cereal, solutions with acceptable electrolyte composition can be prepared from ingredients commonly found in the home. However, in international studies, mixing errors are frequently seen with preparation of these solutions ^{26 ,28} Errors have also been seen in US trials. In 1 US study, nurses, using measuring spoons and graded glasses, produced solutions with sodium concentrations ranging from 25 to 103 mmol/L.²⁹ Dangerous mixing errors were found when homemade solutions were prepared by US inner-city families in another clinical trial.³⁰ Homemade solutions, even when correctly prepared, were of low palatability and were frequently refused by study children.³⁰

Oral electrolyte solutions sold as packets of powder requiring preparation are produced in the United States by the Jianas Brothers (Kansas City, Mo), Cera Products (Jessup, Md), and Pharmacia & Upjohn Inc (Peapack, NJ) (Table 4). Some have the advantages of lower cost, and all have a long shelf life before mixing. Provider surveys indicate that these solutions are rarely recommended or dispensed by US practitioners.^{5 ,22} Provider concerns may include availability, mixing errors, and willingness of caretakers to use these solutions.

With regard to availability, Kao-Lectrolyte (Pharmacia & Upjohn Inc) is commercially available at a cost comparable with Pedialyte. The others are less expensive. These lower-cost products are often purchased by outpatient providers and acute care facilities and dispensed when treating children with gastroenteritis. They could also be provided at health maintenance visits to be kept at home for use in time of need.

There is little evidence of clinically significant error by caregivers preparing current packet-type solutions. The US Public Health Service has been dispensing WHO-ORS packets to ambulatory patients on the Fort Apache Indian reservation in Whiteriver, Ariz, since 1976. When evaluated 5 years after introduction, not a single case of hypernatremia had been observed in more than 1500 ambulatory patients with diarrhea given WHO-ORS packets.³¹ Meyers et al³⁰ analyzed the sodium concentration of solution prepared by US inner-city families given packets of a cereal-based ORS. Of 66 families, only 2 prepared a potentially hypernatremic solution. One error did not involve reconstitution; the parent had added salt to prepared solution, reportedly to enhance flavor. In both cases, child recipients had normal serum sodium values. Additional data from the Whiteriver reservation reveal that provision of verbal and written instructions, along with a graded container for preparation, can enhance reconstitution accuracy.³²

The convenience of a commercially prepared solution did not seem paramount to most caretakers enrolled in our study. When shown both solutions at study enrollment, many were willing to pay almost as much for WHO-ORS as for C-ORS. There was no difference in satisfaction with time needed to prepare the solutions. Perhaps caretakers of infants and small children are accustomed to solution preparation. They have likely prepared powdered or concentrated formulas for infants and noncarbonated beverages for children with great frequency.

The families enrolled in our study were very willing to prepare WHO-ORS. Indeed, more ORS packets were opened by families receiving WHO-ORS than by families receiving C-ORS. Why this occurred remains speculative. This finding is not likely related to severity or duration of illness, as these measures were not significantly different between the groups. It is possible that caretakers using the WHO-ORS perceived it as a "new" product and administered it with greater enthusiasm than those using C-ORS. If the WHO-ORS was indeed easy to prepare and administer and well-accepted by study children, consumption of a greater quantity could have resulted.

Nonetheless, caretakers found WHO-ORS more satisfactory in terms of overall satisfaction and satisfaction with the solution's cost relative to benefit. There was no difference in satisfaction with time needed to prepare the solution or with its appearance or ease of administration to the child. Our results suggest that caretakers of children aged 3 to 48 months are quite willing to prepare and use this solution.

This study has some limitations. Our study population was drawn from outpatient sites serving housestaff training programs. Perhaps families attending these clinics are more open to alternative treatment modalities than families seeking care in nonacademic sites.

The nonblinded nature of the study may have introduced bias. Families were shown both solutions before enrollment to provide a visual idea of what was expected of them before giving consent. They may have been assigned to receive the solution they preferred less, biasing their evaluation. However, most enrollees were familiar with Pedialyte before enrollment. Had familiarity biased satisfaction, one would have expected greater satisfaction with Pedialyte instead of the WHO-ORS.

The desired sample size of 65 subjects per group was not quite attained. However, our study sample of 47 and 50 per group rules out a 15% difference in overall satisfaction between groups with a power exceeding 70%. Our sample size calculations were based on an original hypothesis of equal satisfaction between the groups. In actuality, the WHO-ORS was received with greater satisfaction than C-ORS, with a highly significant absolute difference of 36% in overall satisfaction.

The solutions had a slightly different composition. Could one have actually diminished the duration of diarrhea in a superior fashion, leading to increased satisfaction? At study completion, a similar proportion in each group continued to have diarrhea; however, the trend was for more in the WHO-ORS group to have diarrhea at the follow-up interview (47% vs 33%). The finding of greater satisfaction among the WHO-ORS group does not substantiate this concern.

Caretaker satisfaction could be influenced by the child's illness pattern during the study period, with caretakers expressing lower satisfaction ratings if their child remained ill. We found no relationship between satisfaction and persistence of diarrhea at study completion. Also, no relationship existed between the number of packets/bottles opened nor with stool frequency and satisfaction. From this, we infer no impact on illness duration or severity when measured at 2 days on satisfaction with the solution.

Our study population included primarily low- to middle-income families participating in a governmental medical assistance program. It remains unknown if willingness to use and satisfaction with the WHO-ORS would be similar for higher-income, commercially insured families. We believe our results should encourage use of the WHO-ORS at least by providers serving a population similar to the one studied.

This randomized clinical trial reveals that caretakers of US children receiving the WHO-ORS for outpatient treatment of acute diarrhea were more satisfied with this solution than a comparable group receiving a C-ORS. Fear of caretaker dissatisfaction need not be a barrier to use of the WHO-ORS in the United States. Increased use of this simple, inexpensive treatment could save health care dollars and broaden access to effective oral rehydration and prevention of dehydration for countless children.

Accepted for publication January 31, 2000.

This study was supported by a grant from the Thomas Wilson Sanitarium, Baltimore, Md (Dr Ladinsky).

Solutions used in the study were donated by Ross Nutritionals, Columbus, Ohio (Pedialyte) and the Jianas Brothers, Kansas City, Mo (WHO-ORS).

Presented in part at the Annual Meeting of the Ambulatory Pediatric Association, New Orleans, La, May 3, 1997.

Corresponding author: Morissa Ladinsky, MD, Division of General Pediatrics, Columbus Children's Hospital, 700 Children's Dr, Columbus, OH 43205.