Infectious diarrhea is a leading cause of infant mortality in developing countries. During the last decades the World Health Organisation (WHO) and the United Nations Children's Fund have incorporated oral rehydration therapy (ORT) as the cornerstone of their child-survival efforts and recommended its widespread implementation as an effective, simple, and inexpensive therapy. Although diarrhea is not the overwhelming health problem in the developed countries that it is in developing nations, its importance should not be minimized. Acute gastroenteritis remains a major cause of morbidity and hospitalization in developed countries (1,2). Children younger than 5 years have one to two infections per year, resulting in 25 million yearly episodes, 1.5 million medical consultations, and 200,000 hospitalizations in the United States (3). The financial aspects are very important, as recent data indicate that acute gastroenteritis accounts for 3% of all hospital payments and 2% of all outpatient costs for this age group (2). Sadly, mortality is still at an unacceptable level and nearly all of these deaths could be prevented. Overall, current treatment could be improved. This review will explore the barriers to widespread implementation of ORT and nutritional management in industrialized countries.
SOME HISTORICAL BACKGROUND
To improve understanding of the actual situation, it is important to consider the changing views on the optimal treatment of the condition. Many practicing physicians today were trained at a time when it was thought that children with acute gastroenteritis should undergo therapeutic starvation and have nothing by mouth for 24 hours to allow for “bowel rest.” “Regrading,” the gradual reintroduction of increasing amounts of special milk formula followed this period of rest. In many hospitals, intravenous fluid therapy became an established practice at the period of admission. The speed of realimentation was adjusted by closely observing produced stools. Most milk formulas were high in protein and low in lactose content. Special diets low in fat and indigestible fibers (e.g., the BRAT diet, with banana, rice, apple, and toast/tea) were standard procedures for older children. This teaching dates back to 1926 when Powers reported on the treatment of intestinal intoxication of infants (4). He supported transfusions of blood or fluids and dietary therapy with starvation. In the 1940s, dietary therapy was adjusted, taking into account the first observations of a limited digestive capacity for fat, lactose, and sucrose in acute infectious diarrhea. Formulas designed for realimentation were constituted with a low content of these nutrients.
Modern ORT began in the early 1950s and was first used in the United States. The solution was based on Darrow's (5) careful balanced studies of sodium, potassium, and alkali. In Baltimore, Harrison (6) added glucose to this solution for nutritional reasons, to prevent ketosis, and successfully used the solution for rehydration. General introduction of ORT was very slow to occur, achieved only after the scientific discovery of the coupled intestinal transport of sodium and glucose and the impressive results of oral rehydration solutions (ORS) combating dehydration in Asiatic cholera patients in the late 1960s.
During the past 20 years, the WHO has been involved in an important and very successful task force to promote the formulation, production, distribution, and widespread implementation of ORT in developing countries. In industrialized countries, the speed of introducing ORT was slow. It was initially seen as a kind of reverse transfer of technology, a simple third world therapy (“the underutilized solution”) applied to a modern medical environment. Outdated concepts based on number and aspects of stools had to change to a new framework with treatment of dehydration as the key issue. In Western countries, most children with gastroenteritis are not dehydrated and refuse to take the salty solution. With these observations, professionals started to question the application of ORT. Producers were developing solutions with very high glucose concentrations to ameliorate its taste. High-glucose solutions were reported to cause dangerous osmotic diarrhea with hypernatremia (7). Because fecal sodium losses in children with rotavirus gastroenteritis are lower compared with losses in cholera patients, the composition of the WHO solution was debated. Animal studies and later clinical trials in industrialized countries confirmed the efficacy of a low-osmolar hypotonic solution (8).
The debate on composition prompted the American Academy of Pediatrics and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) to issue recommendations on the composition of ORS and on posttreatment feeding based on careful review of available scientific data (9–12). In contrast with the WHO solution at that time, ESPGHAN advised a hypotonic (low-sodium) solution. The World Health Organization and ESPGHAN concur on their recommendations for a short period of rehydration, realimentation with normal feeding, and continuing use of ORS after watery stools. Breast-feeding must be continued at all times. As a general rule, pharmacologic agents should not be used to treat acute gastroenteritis. The use of lactose-free formula in the vast majority of children is unjustified (13). However, if diarrhea does worsen on reintroduction of milk, stool pH and/or reducing substances should be checked and lactose content reduced only if the stool is acid and contains more than 0.5% reducing substances, suggesting lactose intolerance (12).
WE HAVE THE SOLUTION: NOW WHAT'S THE PROBLEM?
An editorial in 1992 with this title commented on the situation in the United States of health care providers, parents, and insurance companies' poor acceptance of recommended guidelines (14). Using a questionnaire, Snyder (15) found that less than 30% of responding physicians used a solution for rehydration that had the recommended composition. Many of the respondents advised rehydration with high-osmolar clear liquids, such as apple juice. Mild or moderate vomiting was the most common (50%) reason given for withholding ORT. In another survey, Bezerra et al. (16) found that few pediatricians or family practitioners followed other AAP's recommendations. Only 2.3% rehydrated in less than 6 hours, recommended by the guidelines. Also 62% of physicians recommended a lactose-free formula and dilution of formula for more than 1 day. In 1994, another study of physician practice demonstrated that many pediatricians failed to comply with American Academy of Pediatrics guidelines, not using ORT in moderate (30%) or severe (66%) dehydration (17). In this study, it was not lack of ORT knowledge that influenced physicians' daily practice. Lack of convenience in the practice setting, staff preferences for IV therapy, and financial incentives were important barriers to ORT.
In Israel, a questionnaire revealed that pediatricians use ORS appropriately (18). However, when asked about realimentation practice, 37% of pediatricians said they stopped feeding in mild diarrhea, 83% recommended the BRAT diet, and 55% avoided milk products. In a community-based survey of home-treatment practices in Finland, Rautanen et al. (19) reported on the use of water and homemade juices as the primary or an additional drink in mild diarrhea. In more severe cases, ORS was started at home. Of hospitalized patients, 70% had received ORS before admission.
Data from a review of randomized trials further supported the safety and efficacy of ORT in developed countries (20). Failure of ORT, defined as the need to rehydrate children intravenously, is infrequent (3.6%). In addition, the rate of hypernatremia and hyponatremia did not differ when compared with children rehydrated intravenously.
PILLARS OF GOOD TREATMENT
Current recommendations for treatment in Europe are summarized in the “Nine Pillars of Good Treatment” put forward by the ESPGHAN Working Group on Acute Diarrhea (Table 1) (21). In a recent multicenter study performed in 29 European countries, we investigated how closely treatment follows these recommendations (21). For each country, a national coordinator with recognized expertise in the field was recruited. The coordinators were instructed to randomly select physicians from national databases of the professional organizations. The study was based on a questionnaire that addressed the management of a 6-month-old infant with a 3-day history of mild-to-moderate gastroenteritis. The hypothetical infant was 5% dehydrated. There were no special indications for hospital admission. The infant's diet consisted of a cow's milk–based, lactose-containing formula and solids. Each coordinator was asked to recruit an equal number of responses from primary care physicians and hospital-based physicians. The data were collected at a national level and separately analyzed for Western Europe (WE) and Central and Eastern Europe (CEE) taking into account historical differences in health care systems, in particular differences in the organization of primary care.
Almost 3,000 questionnaires were analyzed regarding responses to the Nine Pillars. Eighty-four percent of responding physicians would use ORS for rehydration in the situation described, with 66% using the recommended hypotonic solution. Only 16% would follow the guidelines and rehydrate in 3 to 4 hours. Forty-five percent would rehydrate in a 3-to 6-hour period (WE, 35%; CEE, 60%), and 17% (WE, 23%; CEE, 9%) would extend this period to 12 to 24 hours. Rapid reintroduction of the previous diet was not common, only 21% would restart the diet after 3 to 4 hours. Twenty-one percent would advise reintroduction of solids only after 48 hours. After rehydration, only 43% of responding physicians would start with an undiluted formula. Only 36% (WE, 45%; CEE, 23%) would use normal lactose-containing formula. Special formulas were popular. Contrary to the guidelines, 35% (WE, 30%; CEE, 42%) would use a lactose-free formula and 19% (WE, 12%; CEE, 28%) a lactose and milk protein–free product. If the child were breast-fed, a large majority would continue lactation from the beginning of treatment (77%). Supplementation with ORS to replace ongoing losses from watery diarrhea would be advised by only 37% (WE, 30%; CEE, 46%) of physicians. Recommendation of unnecessary medication is still widely practiced. Many responders consider use of antidiarrheal drugs. Twenty-two percent (WE, 9%; CEE, 41%) would give smectite, 3% (WE, 1%; CEE, 5%) homeopathic drugs, and only 56% (WE, 72%; CEE, 46%) would not consider antimicrobial drugs in a situation as was described in the case history. Only a few physicians would use opiates, loperamide, chlorpromazine, or bismuth subsalicylate.
The results of this survey suggest that with the exception of recommending ORS for rehydration and continuing breast-feeding, only a minority of European physicians follow the guidelines for optimal management. Significant differences were found between (often neighboring) countries. The best overall answers were obtained from physicians in Finland, Portugal, Georgia, Israel, and Slovenia. Rehydration with chicken broth or clear fluids, including tea, cola, and fruit juice, is still popular in some countries. In other countries, homemade ORS from sugar and salt is popular, despite significant errors in composition that may occur during preparation. The greatest deviations from recommended practice were related to the time of refeeding and the type of diet prescribed. Historical treatment with fasting, dilution of formula, and special formulas are still widespread. Even without beneficial effects, these erroneous practices persist today in many communities. We were worried to see so many expensive and unnecessary recommendations made by physicians in countries with lower budgets for health care. Special formula and medication are popular in many CEE countries. A particular source of concern is the overuse of antimicrobial drugs by the majority of surveyed Eastern European physicians. After this study, many national coordinators have presented the data locally to compare their country's score with the rest of Europe.
PHYSICIANS' ATTITUDES TOWARD GUIDELINES
All surveys suggest that changes in traditional treatment is difficult and slow to realize. Guidelines can be defined as systematically developed statements to assist practitioner decisions about appropriate health care for special clinical circumstances (22). Physicians often feel that others impose guidelines, and, in fact, we should realize that the intentions of the people who produce guidelines may differ considerably (Table 2). When clinicians feel that recommendations are imposed, they will usually react with strong aversion and will find arguments to frustrate dialogue.
Little is known about pediatricians' attitudes toward guidelines. Flores at al. (23) used a cross-sectional mail survey in all American states and found that clinical practice guidelines of the American Academy of Pediatrics are used more frequently among general pediatricians who work in practices within health maintenance organizations, who are nonwhite, and who are used significantly less among practices seeing large number of patients (23). No correlation was found for years in practice, sex, and regional location of practice. When general pediatricians were asked to rank their use of nine clinical practice guidelines, guidelines for asthma, hyperbilirubinemia, and otitis media were used more frequently than practice guidelines for gastroenteritis. In fact, only 34% of the general pediatricians in this study were familiar with the existence of clinical practice guidelines for gastroenteritis. In contrast, 88% used the guidelines for treatment of asthma. Pediatricians found it easier to give arguments for not using guidelines than to mention their applicability in daily practice. For the busy clinician, it would seem that guidelines should be simple, flexible, rigorously tested, not used punitively, and motivated by desire to improve quality not reduce costs (23).
DO GUIDELINES CHANGE BEHAVIOR?
Research groups have reported the positive effects of guidelines measured in a research setting with selected groups (24). This does not necessarily mean that guidelines will improve performance or outcome in the unselected target group of professionals. Grimsaw and Russell (24) concluded that the probability of a guideline being effective depended on three factors, summarized in Table 3. This table shows that the most effective guidelines are developed locally by the people who will use them, introduced as part of a specific educational intervention, and implemented through a patient-specific prompt that appears at the time of consultation (22). Further research has identified a number of barriers to the application of guidelines. These include disagreement between experts, lack of appreciation of evidence by the target group, defensive medicine, failure of patients to accept the changes, and lack of appropriate feedback (22).
NEED FOR BETTER TREATMENT
Successful implementation of guidelines is dependent on cooperation among health care providers, parents, health care administrators, professional organizations, primary care physicians, and professionals working in emergency departments (3). Oral rehydration should be seen as a safe, efficient, and inexpensive treatment for dehydration. Training should be provided for all professionals involved. Oral rehydration solution should be included in all pediatric formularies and should be fully reimbursed. Preventive strategies include educational promotion of ORT as part of baby health care visits, easy availability of ORS, and early start in episodes of gastroenteritis.
In emergency departments, an intravenous cannula should be inserted only in rare situations when ORT is contraindicated. Vomiting children rarely require intravenous treatment if small portions of ORS are gently provided. In more pronounced vomiting and in children who persistently refuse oral intakes, rehydration by nasogastric tube is safe (25). Oral rehydration therapy will often require a strong advocate in the department and a staff that will critically consider most cases of intravenous rehydration as failures of oral rehydration. Oral rehydration therapy should be the simple solution, and not the underused solution in the modern medical environment because it is considered too simple.
IMPROVEMENTS IN NEAR FUTURE?
Although ORT is widely recognized as a good treatment for dehydration, it has no beneficial effect on stool output. With ORT, fecal water losses may even temporally increase, seemingly a contradictory effect. Parents may have difficulties appreciating ORT and may consider other options. Most will favor therapeutic interference resulting in reduction of fecal losses, diminished watery stools, and shortened diarrhea episode. Certain probiotics will reduce the duration of rotavirus gastroenteritis (26). Newly developed antisecretory drugs (e.g., racecadotril) may have the potential for reducing stool output (27). Trials with zinc supplementation are promising in malnourished Bangladeshi children with gastroenteritis (28). Studies addressing zinc supplementation in industrialized countries are needed. Studies with patients that investigate extra water absorption in the colon confirm the current Pillars of Good Treatment (29). Short-chain fatty acids, which are produced in the colon from nonabsorbed carbohydrates, enhance sodium absorption and passive water transport. The addition of amylase-resistant starch to standard ORS reduces fecal fluid losses and shortens the duration of diarrhea in adult cholera patients (29). In a constant effort to improve treatment, the ESPGHAN Working Group has started a multicenter study with a mixture of fermentable fibers added to ORS for European children with acute gastroenteritis.
In the last decades, modern ORT has dramatically changed therapeutic options for children with infectious gastroenteritis. In contrast with developing countries, the introduction of ORT in industrialized nations has been relatively slow. Although most physicians are now familiar with ORS for rehydration, surveys from many countries demonstrate that current therapy could be greatly improved. If guidelines were better applied, this could result in a better and less costly treatment for children with acute diarrhea. In many places, we need physicians to promote ORT as the best, the safest, and the least expensive treatment. In industrialized countries, treatment failures often reflect a lack of interest or knowledge about ORT. Achieving wide application of current guidelines will require “careful attention to the principles of change management: in particular, ...leadership, energy, avoidance of unnecessary uncertainty, good communication, and, above all, time”(22).
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