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Epinephrine for bronchiolitis

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Abstract

Background

Bronchodilators are commonly used for acute bronchiolitis, despite uncertain effectiveness.

Objectives

To examine the efficacy and safety of epinephrine in children less than two with acute viral bronchiolitis.

Search methods

We searched CENTRAL (2010, Issue 3) which contains the Acute Respiratory Infections Group's Specialized Register, MEDLINE (1950 to September Week 2, 2010), EMBASE (1980 to September 2010), Scopus (1823 to September 2010), PubMed (March 2010), LILACS (1985 to September 2010) and Iran MedEx (1998 to September 2010).

Selection criteria

We included randomized controlled trials comparing epinephrine to placebo or another intervention involving children less than two years with acute viral bronchiolitis. Studies were included if the trials presented data for at least one quantitative outcome of interest.

We selected primary outcomes a priori, based on clinical relevance: rate of admission by days one and seven of presentation for outpatients, and length of stay (LOS) for inpatients. Secondary outcomes included clinical severity scores, pulmonary function, symptoms, quality of life and adverse events.

Data collection and analysis

Two review authors independently screened the searches, applied inclusion criteria, assessed risk of bias and graded the evidence. We conducted separate analyses for different comparison groups (placebo, non-epinephrine bronchodilators, glucocorticoids) and for clinical setting (inpatient, outpatient).

Main results

We included 19 studies (2256 participants). Epinephrine versus placebo among outpatients showed a significant reduction in admissions at Day 1 (risk ratio (RR) 0.67; 95% confidence interval (CI) 0.50 to 0.89) but not at Day 7 post-emergency department visit. There was no difference in LOS for inpatients. Epinephrine versus salbutamol showed no differences among outpatients for admissions at Day 1 or 7. Inpatients receiving epinephrine had a significantly shorter LOS compared to salbutamol (mean difference -0.28; 95% CI -0.46 to -0.09). One large RCT showed a significantly shorter admission rate at Day 7 for epinephrine and steroid combined versus placebo (RR 0.65; 95% CI 0.44 to 0.95). There were no important differences in adverse events.

Authors' conclusions

This review demonstrates the superiority of epinephrine compared to placebo for short-term outcomes for outpatients, particularly in the first 24 hours of care. Exploratory evidence from a single study suggests benefits of epinephrine and steroid combined for later time points. More research is required to confirm the benefits of combined epinephrine and steroids among outpatients. There is no evidence of effectiveness for repeated dose or prolonged use of epinephrine or epinephrine and dexamethasone combined among inpatients.

Resumen

Antecedentes

Epinefrina para la bronquiolitis

Los broncodilatadores se usan comúnmente para la bronquiolitis aguda, a pesar de que su efectividad es incierta.

Objetivos

Analizar la eficacia y la seguridad de la epinefrina en niños menores de dos años de edad con bronquiolitis viral aguda.

Estrategia de búsqueda

Se realizaron búsquedas en CENTRAL (2010, Número 3) que contiene el Registro Especializado de Ensayos Controlados del Grupo Cochrane de Infecciones Respiratorias Agudas (Acute Respiratory Infections Group's Specialized Register), MEDLINE (1950 hasta la segunda semana de septiembre, 2010), EMBASE (1980 a setiembre de 2010), Scopus (1823 a setiembre de 2010), PubMed (marzo de 2010), LILACS (1985 a setiembre de 2010) e Iran MedEx (1998 a setiembre de 2010).

Criterios de selección

Se incluyeron ensayos controlados con asignación aleatoria que comparaban la epinefrina con placebo u otra intervención que incluía a niños menores de dos años con bronquiolitis viral aguda. Los estudios se incluyeron cuando los ensayos presentaban datos sobre al menos una medida de resultado cuantitativa de interés.

Se seleccionaron las medidas de resultado primarias a priori, sobre la base de la relevancia clínica: tasa de ingreso en los días uno y siete de la presentación para los pacientes ambulatorios, y duración de la estancia hospitalaria para los pacientes hospitalizados. Las medidas de resultado secundarias incluyeron puntuaciones clínicas de la gravedad, la función pulmonar, los síntomas, la calidad de vida y los eventos adversos.

Obtención y análisis de los datos

Dos revisores analizaron las búsquedas, aplicaron los criterios de inclusión, evaluaron el riesgo de sesgo y calificaron las pruebas de forma independiente. Se realizaron análisis separados para los diferentes grupos de comparación (placebo, broncodilatadores sin epinefrina, glucocorticoides) y para el ámbito clínico (hospitalario, ambulatorio).

Resultados principales

Se incluyeron 19 estudios (2 256 participantes). La epinefrina versus placebo entre los pacientes ambulatorios mostró una reducción significativa de los ingresos en el Día 1 (cociente de riesgos [CR] 0,67; intervalo de confianza [IC] del 95%: 0,50 a 0,89) pero no en el Día 7 después de la visita al servicio de urgencias. No hubo diferencias en la duración de la estancia hospitalaria para los pacientes hospitalizados. La epinefrina versus salbutamol no mostró ninguna diferencia entre los pacientes ambulatorios en cuanto a los ingresos en el Día 1 o 7. Los pacientes hospitalizados que recibieron epinefrina tuvieron duraciones de la estancia hospitalaria significativamente más cortas en comparación con el salbutamol (diferencia de medias −0,28; IC del 95%: −0,46 a −0,09). Un ECA amplio mostró una tasa de ingresos significativamente más corta en el Día 7 para la combinación de epinefrina y esteroide versus placebo (CR 0,65; IC del 95%: 0,44 a 0,95). No hubo diferencias importantes en los eventos adversos.

Conclusiones de los autores

Esta revisión demuestra la superioridad de la epinefrina comparada con el placebo en cuanto a los resultados a corto plazo para los pacientes ambulatorios, en particular en las primeras 24 horas de atención. Las pruebas exploratorias de un único estudio indican los beneficios de la combinación de epinefrina y esteroide para los puntos temporales posteriores. Se necesita más investigación para confirmar los beneficios de la combinación de epinefrina y esteroides entre los pacientes ambulatorios. No existen pruebas de efectividad para las dosis repetidas o el uso prolongado de epinefrina o epinefrina más dexametasona en pacientes hospitalizados.

Traducción

Traducción realizada por el Centro Cochrane Iberoamericano

Plain language summary

Epinephrine for acute viral bronchiolitis in children less than two years of age

Bronchiolitis is the most common acute infection of the airways and lungs during the first years of life. It is caused by viruses, the most common being respiratory syncytial virus. The illness starts similarly to a cold, with symptoms such as a runny nose, mild fever and cough. It later leads to fast, troubled and often noisy breathing (for example, wheezing). While the disease is often mild for most healthy babies and young children, it is a major cause of clinical illness and financial health burden worldwide. Hospitalizations have risen in high-income countries, there is substantial healthcare use, and bronchiolitis may be linked with preschool wheezing disorders and the child later developing asthma.

There is variation in how physicians manage bronchiolitis, reflecting the absence of clear scientific evidence for any treatment approach. Bronchodilators are drugs that are often used for asthma attacks to relax the muscles in the airways so that breathing is easier. Epinephrine is one type of bronchodilator. With several new trials having been published since the 2004 publication of this Cochrane Review it is important to incorporate the most recent evidence.

Our systematic review found 19 studies involving 2256 children that use epinephrine for the treatment of bronchiolitis in acute care settings. When comparing epinephrine with placebo, no differences were found for length of hospital stay but there is some indication that epinephrine is effective for reducing hospital admissions. Exploratory results from one large, high-quality trial suggest that combined treatment with systemic glucocorticoids (dexamethasone) and epinephrine may significantly reduce admissions. There is insufficient evidence to support the use of epinephrine for the treatment of bronchiolitis among children admitted to the hospital.

The evidence shows no important differences in adverse effects with epinephrine over the short-term with long-term safety not being assessed. Some limitations of this review include the quality of the included studies and inconsistent timing of measurement across studies which limited the number of children included in some meta-analyses. Further research is needed to confirm the efficacy, applicability and long-term safety of epinephrine as a treatment for bronchiolitis.

In summary, our systematic review provides evidence that epinephrine is more effective than placebo for bronchiolitis in outpatients. Recent research suggests combined epinephrine and steroids may be effective for outpatients. There is no evidence to support the use of epinephrine for inpatients.

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