Bronchiolitis Literature Review
- Although a variety of medications and therapies have been used and studied for treatment of bronchiolitis, the only thing everyone agrees on is that the mainstay for treatment of bronchiolitis is supportive care with fluids and humidified oxygen.
- Other treatment modalities that have been widely used include bronchodilators (beta2-agonists), racemic epi (alpha-agonist) and corticosteroids (systemic or inhaled)
- The diversity of accepted practices have inspired some authors to develop practice guidelines based on the available evidence and examine the impact of implementation of these guidelines on physician practice and patient outcomes
- The following is a summary of the available evidence for each medication and for practice guidelines, starting with background, reviewing the evidence, and followed by suggestions on using this evidence to guide treatment.
Two meta-analyses have been published recently in an attempt to synthesize these confusing data:
- Kellner et al analyzed RCTs of bronchodilators in children with first time wheezing, a total of 4 outpatient and 3 inpatient studies were used. They found a short-term, modest but statistically significant improvement in "clinical score" (ie: wheezes, retractions, respiratory rate, distress, etc) with bronchodilators. No difference was found in hospitalization rate or oxygen saturation. Interestingly, when they included trials that used patients with recurrent wheezing as well, the results were more heterogeneous, suggesting that these patients may have more of a response to bronchodilators (ie: include more children with asthma)
- Flores et al included RCTs of inhaled bronchodilators in first-time or recurrent wheezers, a total of 5 outpatient and 3 inpatient trials. They found no impact on hospitalization, respiratory rate or oxygenation. The authors concluded that no evidence presently exists for the routine use of bronchodilators in bronchiolitis, but that further studies are needed to evaluate whether certain populations of patients may benefit from these medications.
Bronchodilators have not been shown to be effective in reducing clinical symptoms or hospitalizations in patients with bronchiolitis. However, further study is needed to determine their usefulness in specific populations of patients, in particular those with recurrent wheeze or reactive airway disease. A trial of bronchodilators may be warranted in patients with recurrent wheeze or in whom the diagnosis of asthma is suspected, but the treatment should not be repeated if no response.
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A Medline search revealed 5 randomized controlled trials of racemic epinephrine in the treatment of acute bronchiolitis. Both inpatient and outpatient trials reported a statistically significant short-term difference in improvement in clinical score and oxygen saturation with epinephrine when compared with placebo and beta-2 agonists. One outpatient study (Menon, 1995) showed a decreased hospitalization rate with epinephrine treatment. None of these studies showed a statistically significant decrease in length of stay in hospitalized infants with bronchiolitis.
Short-term symptomatic improvement has been shown with use of nebulized epinephrine in some patients with bronchiolitis. However, the clinical impact of these results is unclear, as significant improvement in length of stay has not been shown. A trial of therapy may be warranted, as some patients may experience short-term improvement.
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Theoretically, the anti-inflammatory action of steroids should be helpful in alleviating symptoms of bronchiolitis and reducing symptom duration, but individual RCTs have failed to demonstrate conclusive benefit.
Garrison et al (2000) published a meta-analysis of RCTs of systemic corticosteroids in hospitalized infants with bronchiolitis. They looked at DOS-LOS, clinical scores and oxygen saturation as outcome measures. They also performed a subgroup analysis looking at studies that excluded patients with a previous history of wheezing. They found statistically significant improvements in both clinical symptom scores and DOS-LOS in patients treated with corticosteroids. In a subgroup analysis of studies which excluded patients with previous wheezing, the difference in DOS-LOS was not statistically significant.
Systemic corticosteroids have been shown to produce earlier clinical improvement and shorter hospital stays (mean difference in length of stay - .43 days, mean difference in clinical score at 24 hours after treatment of 1.62 on a scale of 1-12) in a meta-analysis of trials in infants with bronchiolitis. The effect appears to be greatest when patients are sicker, and when the cohort of patients includes a group of patients who have recurrent wheezing (ie: those that later develop asthma).
Could steroids during an attack of bronchiolitis reduce the associated inflammation and lung damage, thereby reducing incidence of subsequent wheezing? The results are mixed. One study failed to show long-term reduction in wheezing/asthma after short-course oral corticosteroid treatment (Berger, 1998), while another showed that inhaled steroids during and after an acute episode of bronchiolitis in hospitalized infants resulted in reduced incidence of a diagnosis of asthma at 2 years of follow-up (Kajosaari, 2000). Interesting implications, but further study is needed.
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Hospital admissions have been increasing in the last two decades, with a 2.4-fold increase in admissions over the period of 1980-1996 (Shay, 1999). Treatment practices for management of bronchiolitis vary widely and are slow to change based on new evidence.
Perlstein et al (1999) reviewed cases of patients admitted with bronchiolitis in Cincinnati from 1993-1996 and found that treatment practices varied widely, and that hospital admission had been increasing over the 4-year period. They formed a 12 member team which produced an evidence-based clinical practice guideline for the hospitalization and care of infants <=1 year old presenting with first-time episode of bronchiolitis. Their recommendations included a trial of inhaled epinephrine and/or bronchodilators in select patients, with continuation of therapy only if improvement is documented within 60 minutes of the first inhalation. They did not recommend routine use of RSV diagnostics, chest X-ray, bronchodilators or systemic/inhaled corticosteroids.
Discharge criteria included respiratory rate <80, oxygen requirement of <1/2 L, and toleration of oral feeds and medications. After implementation of these guidelines, the authors reported a decrease in admissions of 29%, a decrease in LOS of 0.5 days, a decrease in CXR and RSV washes performed, and a decrease in beta-agonist administration of 20%. Mean hospital costs due to bed use decreased by 37%. Satisfaction with hospital performance was similar in the two groups, and there was no increase in readmissions to the hospital.
In a slightly different take on this issue, Kini et al (2001) were interested in comparing hospital practice to the Milliman and Robertson guidelines (commercially produced guidelines widely used by managed care organizations) for goal length of stay (GLOS). The researchers compared the average length of stay for patients with "uncomplicated" bronchiolitis in eight pediatric hospitals during the winter of 89-90 to the Milliman and Robertson guidelines for goal length of stay (1 day). They found that all sites exceeded the GLOS guidelines (in all, 43% of patients stayed longer than one day), even after introduction of the Perlstein practice guidelines (although they did not assess compliance with these guidelines.)
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