An eight-month-old male infant presents with a one-day history of cough, fever, congestion, and a visible increase in respiratory effort, but has no prior history of such symptoms. On examination, the child has tachypnea, diffuse wheezing, and a mildly decreased pulse oximetry reading. His physician diagnoses bronchiolitis and wonders if a nebulized bronchodilator treatment might improve his oxygen saturation and keep him out of the hospital.
Do bronchodilators improve outcomes in infants with a new diagnosis of bronchiolitis who do not have a history of wheezing?
Bronchodilators may transiently improve the clinical status of infants with bronchiolitis and no prior history of wheezing. However, moderately strong evidence shows that key outcomes such as oxygen saturation, need for hospitalization, length of hospitalization, and duration of symptoms are not changed by the use of bronchodilators.1 (Strength of Recommendation = A, based on consistent, good-quality patient-oriented evidence)
Background: Bronchiolitis is an acute, viral lower respiratory tract infection affecting infants and often treated with bronchodilators.
Objectives: To assess the effects of bronchodilators on clinical outcomes in infants with acute bronchiolitis.
Search Strategy: The authors searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2010, Issue 1), which contains the Acute Respiratory Infections Group's Specialized Register, Medline (1966 to March 2010), and EMBASE (2003 to March 2010).
Selection Criteria: Randomized controlled trials comparing bronchodilators (other than epinephrine) with placebo for bronchiolitis.
Data Collection and Analysis: Two authors assessed trial quality and extracted data. Unpublished data were obtained from trial authors.
Main Results: The review included 28 trials (n = 1,912) of infants with bronchiolitis. In 10 inpatient and 10 outpatient studies, oxygen saturation did not improve with bronchodilators (mean difference [MD] = –0.45; 95% confidence interval [CI], –0.96 to 0.05; n = 1,182). Outpatient bronchodilator treatment did not reduce the rate of hospitalization (12 percent in bronchodilator group versus 16 percent in placebo; odds ratio = 0.78; 95% CI, 0.47 to 1.29; n = 650). Inpatient bronchodilator treatment did not reduce the duration of hospitalization (MD = 0.06; 95% CI, –0.27 to 0.39; n = 349). In seven inpatient and eight outpatient studies, average clinical score decreased slightly with bronchodilators (standardized mean difference [SMD] = –0.37; 95% CI, –0.62 to –0.13; n = 1,006).
Oximetry and clinical score outcomes showed significant heterogeneity. Including only studies at low risk of bias significantly reduced heterogeneity measures for oximetry (I2 statistic = 17 percent) and average clinical score (I2 statistic = 26 percent), but had little impact on the overall effect size of oximetry (MD = –0.38; 95% CI, –0.75 to 0.00; P = .05) and average clinical score (SMD = –0.26; 95% CI, –0.44 to –0.08; P = .005). Effect estimates for outpatients were slightly larger than for inpatients for oximetry (outpatients MD = –0.57; 95% CI, –1.13 to 0.00; versus inpatients MD = –0.29; 95% CI, –1.10 to 0.51) and average clinical score (outpatients SMD = –0.49; 95% CI, –0.86 to –0.11; versus inpatients SMD = –0.20; 95% CI, –0.43 to 0.03). Adverse effects included tachycardia and tremors.
Authors' Conclusions: Bronchodilators do not improve oxygen saturation, do not reduce hospital admission after outpatient treatment, do not shorten the duration of hospitalization, and do not reduce the time to resolution of illness at home. The small improvements in clinical scores for outpatients must be weighed against the costs and adverse effects of bronchodilators.
These summaries have been derived from Cochrane reviews published in the Cochrane Database of Systematic Reviews in the Cochrane Library. Their content has, as far as possible, been checked with the authors of the original reviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minor editing changes have been made to the text (http://www.cochrane.org).
Bronchiolitis is an acute infectious illness that starts as an upper respiratory tract infection. It can progress to respiratory distress with signs of bronchiolar obstruction, including wheezing and air trapping.2 This wheezing has resulted in bronchiolitis being treated with interventions known to work in asthma, including bronchodilators and steroids.3 However, unlike asthma, the wheezing of bronchiolitis is caused by inflammation and debris within the airways rather than bronchoconstriction.1
This Cochrane review included a total of 28 randomized controlled trials examining the use of bronchodilators for bronchiolitis in children younger than two years.1 The bronchodilators reviewed included albuterol, salmeterol (Serevent), ipratropium (Atrovent), terbutaline, and adrenergic agents. Studies examining epinephrine or inhaled steroids were excluded from the review. A previous Cochrane review found inadequate evidence to recommend epinephrine therapy for bronchiolitis.4
The primary outcome for the review was oxygen saturation, a physiologic endpoint.1 Secondary patient-oriented outcomes included improvement in clinical score, hospital admission, time to illness resolution, and duration of hospitalization. Inpatient and outpatient studies were included. The authors included 20 studies measuring pulse oximetry. They found no significant improvement in oxygen saturation with use of bronchodilators (mean difference = –0.45; 95% confidence interval [CI], –0.96 to 0.05).
There was a statistically significant difference in the number of infants showing improved clinical scores (odds ratio for no improvement = 0.18; 95% CI, 0.06 to 0.50) and in the magnitude of the improvement (standardized mean difference = –0.37; 95% CI, –0.62 to –0.13) with the use of bronchodilators. The authors noted that the clinical significance of this improvement was highly questionable. Potential bias was introduced by interrater variability within individual trials and by variability among the different clinical scores used in different trials. In addition, there is no evidence that any of the clinical scores used are valid indicators of pulmonary or overall clinical status.
Seven studies with a total of 344 participants evaluated whether nebulized bronchodilators administered to outpatients reduced the rate of hospitalization. There was no significant difference between the bronchodilator and placebo groups in admission rates (12 versus 16 percent, respectively; odds ratio = 0.78; 95% CI, 0.47 to 1.29). Three studies also found no reduction in hospitalization rates in infants treated with oral bronchodilators in the emergency department or at home.
The use of bronchodilators in hospitalized infants with a diagnosis of bronchiolitis did not change the length of stay. The mean difference between bronchodilator and placebo groups was a statistically nonsignificant 0.06 days (95% CI, –0.27 to 0.39). Similarly, the use of bronchodilators did not change infants' duration of illness. Two studies with a total of 269 participants compared oral bronchodilators used at home with placebo. The mean difference between groups was a nonsignificant 0.29 days (95% CI, –0.43 to 1.00). None of the studies using nebulized bronchodilators looked at time to resolution of illness.
Many studies included in this meta-analysis did not evaluate or report adverse effects. Studies that reported adverse effects found them almost exclusively among the participants receiving bronchodilators. Tachycardia, tremor, and jitteriness are commonly described adverse effects of bronchodilators. Additionally, mild hypertension, flushing, cough, and sometimes even decreased oxygen saturation were described in participants receiving bronchodilators.
Although a small, short-term improvement in subjective clinical scores may occur with the use of bronchodilators in infants with bronchiolitis, important outcomes such as hospitalization, oxygen saturation, and duration of illness are not changed. These facts, when combined with the high frequency of adverse effects, make bronchodilators a poor treatment option for infants with a new diagnosis of bronchiolitis and no prior history of wheezing. Bronchodilators continue to be a reasonable option in those infants with a prior history of wheezing.