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From the Division of Pediatric Emergency Medicine, Department of Pediatrics, Children’s Hospital of Philadelphia, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 34th and Civic Center Boulevard, Philadelphia, Pennsylvania
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Objective. To test the hypothesis that the failure rate of ORT would not be >5% greater than the failure rate of IVF. Secondary hypotheses were that patients in the ORT group will (1) require less time initiating therapy, (2) show more improvement after 2 hours of therapy, (3) have fewer hospitalizations, and (4) prefer ORT for future episodes of dehydration.
Methods. A randomized, controlled clinical trial (noninferiority study design) was performed in the emergency department of an urban children’s hospital from December 2001 to April 2003. Children 8 weeks to 3 years old were eligible if they were moderately dehydrated, based on a validated 10-point score, from viral gastroenteritis. Patients were randomized to receive either ORT or IVF during the 4-hour study. Treating physicians were masked and assessed all patients before randomization at 2 and 4 hours of therapy. Successful rehydration at 4 hours was defined as resolution of moderate dehydration, production of urine, weight gain, and the absence severe emesis (
5 mL/kg).
Results. Seventy-three patients were enrolled in the study: 36 were randomized to ORT and 37 were randomized to IVF. Baseline dehydration scores and the number of prior episodes of emesis and diarrhea were similar in the 2 groups. ORT demonstrated noninferiority for the main outcome measure and was found to be favorable with secondary outcomes. Half of both the ORT and IVF groups were rehydrated successfully at 4 hours (difference: –1.2%; 95% confidence interval [CI]: –24.0% to 21.6%). The time required to initiate therapy was less in the ORT group at 19.9 minutes from randomization, compared with 41.2 minutes for the IVF group (difference: –21.2 minutes; 95% CI: –10.3 to –32.1 minutes). There was no difference in the improvement of the dehydration score at 2 hours between the 2 groups (78.8% ORT vs 80% IVF; difference: –1.2%; 95% CI: –20.5% to 18%). Less than one third of the ORT group required hospitalization, whereas almost half of the IVF group was hospitalized (30.6% vs 48.7%, respectively; difference: –18.1%; 95% CI: –40.1% to 4.0%). Patients who received ORT were as likely as those who received IVF to prefer the same therapy for the next episode of gastroenteritis (61.3% vs 51.4%, respectively; difference: 9.9%; 95% CI: –14% to 33.7%).
Conclusions. This trial demonstrated that ORT is as effective as IVF for rehydration of moderately dehydrated children due to gastroenteritis in the emergency department. ORT demonstrated noninferiority for successful rehydration at 4 hours and hospitalization rate. Additionally, therapy was initiated more quickly for ORT patients. ORT seems to be a preferred treatment option for patients with moderate dehydration from gastroenteritis.
Key Words: oral rehydration therapy • viral gastroenteritis • pediatric emergency medicine • dehydration • intravenous fluid therapy • acute gastroenteritis
Abbreviations: ED, emergency department • ORT, oral rehydration therapy • PEM, pediatric emergency medicine • IVF, intravenous fluid therapy • IV, intravenous line • CI, confidence interval
Viral gastroenteritis with subsequent dehydration is a significant health problem facing American children. In the United States, 
10% of hospitalizations in children <5 years old are due to gastroenteritis and dehydration, accounting for nearly 220000 hospitalizations yearly.1 The costs of gastroenteritis with dehydration are high. In 1 year alone, the hospitalization costs for the most common cause of viral gastroenteritis, rotavirus, was $352 million.1 This figure does not take into account numerous other components of the true cost such as emergency department (ED) and primary care provider visits and lost wages.
Oral rehydration therapy (ORT) is recommended by the American Academy of Pediatrics and the World Health Organization as first-line therapy for mild to moderate dehydration.2,3 However, a recent survey revealed that US pediatric emergency medicine (PEM) providers do not use ORT, because they believe it is time-consuming for patients and staff.4 Additionally, PEM providers think parents and referring physicians have expectations for intravenous fluid therapy (IVF).4 Additionally, three quarters of physicians who classified themselves as very familiar with the American Academy of Pediatrics recommendations for ORT report nearly exclusive use of IVF for moderately dehydrated children.5
There are inherent benefits of ORT that make it a desirable therapy. Patients treated successfully with ORT do not require intravenous access, a potentially painful and difficult procedure in young children. Furthermore, parents who learn to administer ORT correctly have acquired a skill that can be used at home for ongoing and future illnesses. However, there are limited data available about ORT in an outpatient setting such as the ED. A recent randomized trial comparing ORT to IVF in children <18 years old revealed that ORT patients had a shorter ED length of stay and less staff time involved.6 However, this study was limited by a lack of masking, lack of a standardized definition of dehydration, and a wide age range of subjects.
We designed this study to test the primary hypothesis that the failure rate of ORT would not be >5% greater than the failure rate of IVF. We chose a noninferiority study design to compare 2 effective and established treatment options. We believed that if ORT was shown to be as effective as IVF, then practitioners might be more likely to adopt it into their practice. Secondary hypotheses were that less time would be involved in initiating ORT, more patients in the ORT group would have improved dehydration scores after 2 hours of therapy than the IVF group, fewer patients in the ORT group would require hospitalization, and more parents in the ORT group would prefer ORT for future episodes of dehydration.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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= 0.62; P = .001). Patients were included if they were moderately dehydrated (dehydration score 3 and <7, corresponding to 5–10% dehydration) with a diagnosis of probable viral gastroenteritis (defined as 3 loose or watery stools in the previous 24 hours), a parent or legal guardian was available to remain with the patient, and there was a phone number at which they could be contacted at 72 hours for follow-up. Patients were excluded for hypotension (systolic blood pressure 2 SDs below the mean for age on 2 repeated measures), duration of illness >5 days (because alternative diagnosis and treatment may be necessary), history of chronic illness that would influence fluid status (eg, renal disease), or malnutrition/failure to thrive/impaired oromotor skills. Patients who received treatment at any ED within the preceding 12 hours or were enrolled in the study previously were also excluded. Patients who met study criteria were approached for written informed consent. After consent, the patient was moved to a 23-hour observation unit in the ED, at which randomization and the 4-hour trial took place. A baseline pretherapy weight without clothing or diapers was obtained on all children. As described in greater detail below, patients were randomized to 1 of 2 treatment groups (ORT or IVF) and rehydrated during the 4-hour study period. Patients in the ORT group received Pedialyte (Abbott Laboratories, Abbott Park, IL) at 50 mL/kg orally over 4 hours if their baseline dehydration score was 3, 4, or 5 and 75 mL/kg if the baseline dehydration score was 6. After instruction on proper ORT techniques from a nurse or nurse practitioner formally trained in ORT, the ORT fluid was administered in equal 5-minute aliquots by the parents. Patients in the IVF group had an intravenous line (IV) placed and received two 20 mL/kg normal saline boluses within the first hour (40 mL/kg total). After the IV boluses were complete, patients were encouraged by nursing staff and parents to drink oral fluids during the subsequent 3 hours. Pedialyte was offered first, but if patients refused or parents requested, water or juice was allowed. An emesis basin was provided to all patients to collect emesis. Any volume of emesis found on the patient’s clothing or hospital linens was estimated using premeasured emesis stains.8 The randomization, treatment start, and treatment completion times were recorded for all patients. Both groups remained in the study for 4 hours. At the end of the second and fourth hours, the child was reweighed without clothing or diapers, and the physician was brought back to perform a 10-point dehydration score. The decision to admit or discharge was made at the completion of the study.
We considered that some patients would not be able to perform ORT and defined inability to perform ORT a priori as vomit 25% of the hourly oral requirement or 6 consecutive oral refusals. These children were considered an ORT failure for the main outcome of successful rehydration at 4 hours and for the criteria for discharge at 2 hours. These children remained in the ORT group for all statistical analyses. An IV was placed, and they were rehydrated with intravenous fluids.
Outcome Measures
The primary outcome was success of treatment in the ED at 4 hours, which was defined as resolution of moderate dehydration (a 4-hour dehydration score 
2, which would indicate mild to no dehydration), weight gain, production of urine output during the trial, and absence of severe emesis (5 mL/kg) during the fourth hour of the trial. The criteria for the primary outcome were chosen to reflect objective reasons that a moderately dehydrated child <3 years old would need additional treatment.
Predefined secondary outcome measures included time to initiate therapy, improvement in the dehydration score after 2 hours of therapy, hospitalization rate, parental therapy preference at 4 hours, and 72-hour ED revisits. The time to initiate therapy was defined as the interval between the randomization time and the treatment start time. After 2 hours of therapy, a PEM-trained physician masked to the treatment assignment performed an evaluation on all patients including a repeat dehydration score. The disposition decision was made after the treatment assignment had been revealed to the treating physician at the completion of the study and was an unmasked secondary outcome measure. Parental preference was assessed after the 4-hour rehydration period by using a survey administered to parents about their therapy preferences. Seventy-two-hour ED-revisit information was obtained through a follow-up phone call to all subjects. If the patient was admitted to the hospital and still an inpatient at 72 hours, they were excluded from this particular analysis, because they were not eligible for a 72-hour ED revisit. All patients remained in the study for a 4-hour period.
Sample Size
Although there were no published data on rehydration in an outpatient setting during the planning of this trial, the published ORT failure rate is 3.4% in an inpatient setting with nasogastric tube use if the patient was unable to take ORT fluid orally.9 Because we did not use nasogastric tubes for patients who were unable to tolerate ORT, we assumed there would be a 20% failure rate of ORT in the ED. Before the start of the study we estimated a need for 50 patients in each group to have 80% power to demonstrate that the failure rate of ORT was lower than or at most no more than 5% greater than the corresponding rate for IVF using a 1-sided 
of .05.
Statistical Analysis
Descriptive analysis techniques were used to compare demographics and historical information of the 2 study groups. Risk differences with 95% confidence intervals (CIs) were used to compare binomial outcomes such as successful treatment at 4 hours and hospitalization rate. t tests were used to evaluate differences in continuous outcomes such as time to initiate therapy. The primary statistical analyses were conducted on an intention-to-treat basis.
Assignment
The subjects were randomized to the treatment groups by using block randomization of variable block sizes. Blocks of 6, 8, and 10 were determined by using a table of random numbers, and randomization within the blocks was also determined by using a table of random numbers. The assignments were kept in a sealed packet with all study-related materials in an area of the ED to which only the nurse practitioners had access. After written informed consent was obtained, the nurse practitioner acquired a packet, the patient was brought to the 24-hour unit, and the sealed treatment assignment was opened.
Masking
The study was single-masked. The subject and family were aware of the treatment assignment; the treating physician was masked. Masking was accomplished for the ORT group by placing a sham IV with a heparin lock taped to the outside of the subject’s hand, a sham IV board, a sham protective covering over the heparin-locked IV, and occasionally a sham bandage on the other hand to give the appearance of 2 IV attempts. For the IVF group, patients had the same equipment, except the IV was actually placed intravenously. To maintain masking, both groups of subjects were taken to a separate treatment room away from all study materials to obtain 2- and 4-hour dehydration scores and weights. No rehydration supplies were visible to the physician making the assessment. The nurses and families were reminded not to disclose the treatment assignment to the physician. To determine the effectiveness of masking, the physicians were asked at the 2- and 4-hour dehydration assessment whether they thought the patient was receiving ORT or IVF or if they were uncertain of the treatment assignment.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Treatment Received
When analyzed according to the treatment received, ORT still demonstrated noninferiority compared with IVF for the main outcome of successful rehydration at 4 hours. Specifically, 60.6% of ORT patients and 61.8% of IVF patients were rehydrated successfully (risk difference: –1.2%; 95% CI: –24.5% to 22.2%). Only 22.7% of subjects in the ORT group required hospitalization, as contrasted with 50% in the IVF group (risk difference: –22.7%; 95% CI: –45.4% to –0.1%). The other secondary outcomes were not different from the intention-to-treat analysis and are not presented.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Dehydration scores after rehydration therapy showed comparable improvements, with >90% of patients in the ORT group and >82% of patients in the IVF group having a 4-hour dehydration score that demonstrated resolution of their moderate dehydration. The majority of patients had made urine by 4 hours, and neither group had severe episodes of emesis during the final hour of the rehydration period. Although the other components of successful rehydration were similar between groups, the IVF group did demonstrate better weight gain than the ORT group, and this difference was statistically significant. It should be mentioned that patients are not routinely reweighed in the ED before discharge. In fact, common clinical features used alone or in combination to determine if a child is ready for discharge include an improved clinical assessment, the production of urine, and the absence of severe emesis, which are reflected in our outcome measure. We do feel, however, that the outcome measure we chose accurately describes the success of rehydration in the ED, because our success rates are comparable to our discharge rates.
Although the individual components of our definition of successful rehydration were met in >80% of cases, the overall success rate was lower, which is likely due to our conservative definition of success as well as the contribution of missing data that placed these patients in the failure category. Additionally, the mean oral intake in the intention-to-treat ORT group was 36 mL/kg. When the patients who were unable to tolerate ORT were excluded from analysis, oral intake increased to 42.8 mL/kg, very close to our 50 mL/kg goal. The results from this study support the concept that there is an inherent benefit to using the gastrointestinal tract for rehydration given the fact that the ORT patients had less fluid intake yet did just as well as the IVF patients.
Furthermore, 2 systematic reviews of rehydration therapy for dehydration from gastroenteritis also found enteral therapy to be as effective as intravenous therapy.9,12 However, most of the clinical trials included in these reviews occurred in inpatient settings, and many took place in developing countries. The trials also lacked masking of treatment assignments, intention-to-treat analyses, and adequate description of randomization. Our trial overcomes many of these prior trial limitations.
Our original definition of success included an oral-intake parameter. However, posthoc, the oral intake was removed from the definition of success, because its presence influenced the study results such that there was a statistical and clinical benefit of ORT over IVF. It was our feeling that the benefit from the oral intake could reflect a bias in that there was a systematic offering of oral fluids to the ORT group but not the IVF group. Although, the IVF group was strongly encouraged to take oral fluids, there was not a requirement for them to do so. We feel that the definition of success as presented in this article is a more objective definition free of bias.
Some limitations of our trial should be noted. The 23-hour observation unit, the site of this study, may be different from the contiguous ED. IV-insertion time was optimized in that randomization occurred in the treatment room with a nurse ready to place an IV if the child was randomized to the IVF group. As a result, there would undoubtedly be an even greater time differential favoring ORT under nonstudy circumstances. However, the underlying aim of the study was to test the 2 treatment options as an efficacy study. The next step would be to conduct an effectiveness study in a more generalizable ED setting. Furthermore, because moist mucous membranes are a component of the dehydration score, oral intake could moisten the mucous membranes and influence measured dehydration scores. However, because both groups were allowed oral intake, minimal bias should have been introduced due to this fact.
Certain factors may affect the generalizability of this trial. Because the study was conducted between 8 AM and midnight, while research personnel were available, patients and parents were more likely to be awake and able to perform ORT. ORT may be less successful in the middle of the night. In addition, the trial was conducted in a pediatric ED in which nurses are extremely skilled in placing IVs even in dehydrated children. Subsequently, IVF may be more difficult to administer in other settings simply due to the difficulty in obtaining intravenous access.
Our study was stopped before reaching the 100-subject goal. The study occurred over 2 gastroenteritis seasons, and after the second season, there was a decline in the number of patients presenting to the ED with probable viral gastroenteritis. Furthermore, with time, the ED staff became more familiar with proper ORT administration, and many children were started on ORT before evaluation for the trial. Family satisfaction with ORT early in the ED course decreased trial participation–consent rates. The loss of clinical equipoise and declining accrual rate led to the early termination of the study. No interim analysis was performed. Still, we were able to demonstrate that ORT is not inferior to IVF in rehydrating moderately dehydrated young children. Although our study refusal rate approached 30%, less than half were due to families refusing ORT, with a similar number not desiring IVF. This result suggests that a therapeutic alliance can be made with families to initiate ORT for dehydration.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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Address correspondence to Philip R. Spandorfer, MD, MSCE, Children’s Hospital of Philadelphia, Division of Emergency Medicine, 34th St and Civic Center Blvd, Philadelphia, PA 19104. E-mail: spandorfer{at}email.chop.edu
No conflict of interest declared.
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REFERENCES |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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