Is racecadotril effective for acute diarrhea in children? -First update. / ¿Es efectivo el racecadotrilo como tratamiento para la diarrea aguda en niños? -Primera actualización.

This article updates the December 2015 Living FRISBEE (Living FRISBEE: Living FRIendly Summary of the Body of Evidence using Epistemonikos), based on the detection of two systematic reviews not identified in the previous version. Gastroenteritis or acute watery diarrhea is usually a self-limited disease, but it is still associated to substantial healthcare costs and remains a frequent demand for medical care. Racecadotril, an intestinal enkephalinase inhibitor, has been used as treatment because it would decrease the duration of acute diarrhea and fluid loss. However there is still no evidence supporting its routine use. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified five systematic reviews including nine randomized trials relevant for our question. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded racecadotril probably reduces the duration of acute diarrhea in pediatric patients, without increasing adverse effects.

Este resumen Epistemonikos (Living FRISBEE: Living FRIendly Summary of the Body of Evidence using Epistemonikos) es una actualización del resumen publicado en Diciembre de 2015, basado en la detección de dos nuevas revisiones sistemáticas que no habían sido identificadas en la versión anterior. La gastroenteritis o diarrea aguda es una enfermedad habitualmente autolimitada, pero que consume recursos sanitarios y constituye un motivo de consulta frecuente en pediatría. El racecadotrilo, un inhibidor de la encefalinasa intestinal, se ha usado como tratamiento porque disminuiría la duración de la diarrea y la pérdida de líquidos, pero no hay evidencia que justifique su uso rutinario. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos cinco revisiones sistemáticas que en conjunto incluyen nueve estudios aleatorizados relevantes para nuestra pregunta. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que el uso de racecadotrilo probablemente disminuye la duración del cuadro de diarrea aguda en población pediátrica y que no se asociaría a mayor tasa de eventos adversos.

[Efficacy of racecadotril vs. smectite, probiotics or zinc as an integral part of treatment of acute diarrhea in children under five years: A meta-analysis of multiple treatments]. / Eficacia del racecadotrilo versus smectita, probióticos o zinc como parte integral del tratamiento de la diarrea aguda en menores de cinco años: meta-análisis de tratamientos múltiples.

RATIONALE: Despite major advances in treatment, acute diarrhea continues to be a public health problem in children under five years. There is no systematic approach to treatment and most evidence is assembled comparing active treatment vs. placebo. OBJECTIVE: Systematic review of evidence on efficacy of adjuvants for treatment of acute diarrhea through a network meta-analysis. METHODS: A systematic search of multiple databases searching clinical trials related to the use of racecadotril, smectite, Lactobacillus GG, Lactobacillus reuteri, Saccharomyces boulardii and zinc as adjuvants in acute diarrhea was done. The primary endpoint was duration of diarrhea. Information is displayed through network meta-analysis.The superiority of each coadjutant was analyzed by Sucra approach. RESULTS: Network meta-analysis showed race cadotril was better when compared with placebo and other adjuvants. Sucra analysis showed racecadotril as the first option followed by smectite and Lactobacillus reuteri. INTERPRETATION: Considering a strategic decision making approach, network meta-analysis allows us to establish the therapeutic superiority of racecadotril as an adjunct for the comprehensive management of acute diarrhea in children aged less than five years.

Grading recommendations in clinical practice guidelines: randomised experimental evaluation of four different systems.

OBJECTIVE: To evaluate the effect of presenting a recommendation in a clinical practice guideline using different grading systems to determine to what extent the system used changes the clinician's eventual response to a particular clinical question. DESIGN: Randomised experimental study. SETTING: Clinician offices and academic settings. PARTICIPANTS: Paediatricians and paediatric residents in private and public practice in Mexico. INTERVENTION: Case notes of a child with diarrhoea and a question about clinician preference for using racecadotril. The same evidence was provided in a clinical recommendation but with different presentations according to the following grading systems: NICE (National Institute for Health and Clinical Excellence), SIGN (Scottish Intercollegiate Guideline Network), GRADE (Grading of Recommendations Assessment, Development and Evaluation) and CEBM (Centre for Evidence-Based Medicine, Oxford). MAIN OUTCOME MEASURE: Mean change in direction from baseline response (measured on a 10 cm visual scale and a Likert scale) and among groups. RESULTS: 216 subjects agreed to participate. Most participants changed their decision after reading the clinical recommendations (mean difference 0.7 cm, 95% CI 0.29 to 1.0; p<0.001). By groups, mean change (95% CI) from baseline was 0.04 (-0.68 to 0.77) for NICE, 0.31 (-0.41 to 1.05) for SIGN, 2.18 (1.48 to 2.88) for GRADE and 0.08 (-0.52 to 0.69) for CEBM (p=0.007 between groups). In a final survey, a small difference was noted regarding the clarity of the results presented with the GRADE system. CONCLUSION: The clinician's decision to use a therapy was influenced most by the GRADE system. TRIAL REGISTRATION NUMBER: NCT00940290.

Use of racecadotril as outpatient treatment for acute gastroenteritis: a prospective, randomized, parallel study.

OBJECTIVE: To compare the efficacy of therapy with racecadotril plus oral rehydration versus oral rehydration alone in children with gastroenteritis in an outpatient setting care. STUDY DESIGN: Prospective, randomized, open and parallel study performed in a Pediatric Emergency Service of a tertiary care hospital. The study included 189 patients, ages 3 to 36 months, with acute gastroenteritis: 94 were administered an oral rehydration solution (OR), 94 received oral rehydration solution plus racecadotril (OR + R). The principal variable studied was the number of bowel movements in 48 hours after initiating treatment. RESULTS: The groups were comparable clinically and epidemiologically at enrollment. No significant differences were found in the number of bowel movements between the 2 groups 48 hours after initiating treatment (4.1 +/- 2.7 bowel movements in the OR group vs 3.8 +/- 2.4 bowel movements in the OR + R group). No differences were found in the average duration of gastroenteritis (4.7 +/- 2.2 days in the OR group, 4.0 +/- 2.1 days in the OR + R group; P = .15). The incidence of adverse events was similar in both groups (19 patients [20.2%] in the OR group, 18 patients [19.1%] in the OR + R group). CONCLUSIONS: In our study group, the use of racecadotril did not improve the symptoms of diarrhea compared with standard rehydration therapy.

Racecadotril in the treatment of acute watery diarrhea in children.

BACKGROUND: Racecadotril (acetorphan), an enkephalinase inhibitor with antisecretory and antidiarrheal actions, is an effective and safe treatment for acute diarrhea in adults and children. Whether treatment with racecadotril and oral rehydration therapy is more effective than treatment with oral rehydration alone in hospitalized children with acute watery diarrhea is not known. METHODS: We treated 135 boys 3 to 35 months of age who had watery diarrhea of five days' duration or less with racecadotril (1.5 mg per kilogram of body weight orally every eight hours) or placebo, in addition to oral rehydration solution. The primary end point was the 48-hour stool output (measured in grams); the total stool output, duration of diarrhea, and total intake of oral rehydration solution were also measured. RESULTS: The mean (+/-SE) 48-hour stool output was 92+/-12 g per kilogram in the racecadotril group and 170+/-15 g per kilogram in the placebo group (P<0.001), a 46 percent reduction with racecadotril. The results were similar among the 73 boys with rotavirus infections. The total stool output was 157+/-27 g per kilogram in the racecadotril group and 331+/-39 g per kilogram in the placebo group (P<0.001). The median duration of diarrhea was significantly less (P<0.001) in the racecadotril group (28 hours regardless of rotavirus status) than in the placebo group (72 and 52 hours, respectively, for rotavirus-positive and rotavirus-negative patients). The intake of oral rehydration solution was significantly lower in the racecadotril group than in the placebo group (P<0.001). Racecadotril was well tolerated; only seven patients taking racecadotril had adverse effects, which were all mild and transient. CONCLUSIONS: In young boys with acute watery diarrhea, racecadotril is an effective and safe treatment.