Acute asthma presentations account for more than 2.1 million Emergency Department (ED) visits annually. In the US, 8.4% of the population is affected by the disease. Current guidelines from the National Heart, Lung, and Blood Institute recommend a minimum of 5 days of oral prednisone to treat moderate to severe asthma exacerbations (NHLBI Guidelines 2007). Oral and parenteral dexamethasone have similar bioavailability, with a duration of action of 72 hours. There has been promising data on dexamethasone for acute asthma from the pediatric literature, as well as a 2-dose regimen in adults. However, due to the strong association with low patient adherence and poor outcomes, a single dose of a long acting oral medication in the ED may help prevent relapse of symptoms.
Is a single dose of oral dexamethasone non-inferior to 5 days of oral prednisone in the treatment of adults with mild to moderate asthma exacerbations?
Patients aged 18-55 years, with a history of asthma, who presented to the ED with an episode of acute asthma requiring more than 1 albuterol nebulizer treatment, and were discharged home.
12mg of oral dexamethasone in the ED plus 4 days of placebo capsules
Prednisone 60mg in ED plus 4 days of 60mg of prednisone
Relapse (defined as an unscheduled return visit to a health care provider for additional treatment for persistent or worsening asthma within 14 days). The upper limit of noninferiority was set at an 8% difference
Prospective, randomized, triple-blinded, controlled, noninferiority single center trial
Age < 18 years or > 55 years, patients without a working telephone number, pregnant women, patient with an allergy to corticosteroids, use of oral corticosteroids 2 weeks before presentation, or severe exacerbations requiring immediate airway intervention such as noninvasive bilevel airway support or intubation, or those admitted to the hospital. Also excluded patients with a history of chronic obstructive respiratory disease, pulmonary fibrosis, HIV/AIDS, congestive heart failure, active varicella, active tuberculosis or diabetes mellitus.
- 1,677 patients were assessed for eligibility
- 465 were randomized to either receive prednisone (238) or dexamethasone (227)
- 376 were included in final analysis (follow up rate: 81%)
- Both groups had similar baseline characteristics, including age, sex, race or ethnicity, asthma severity history, home inhaled steroid use, vital signs, peak flow rates, and ED-based treatments.
- Relapse, or a return visit for asthma within 14 days:
- 12.1% dexamethasone vs 9.8% prednisone
- Absolute difference = 2.3% (95% CI: -4.1% to 8.6%)
- Single dose oral dexamethasone was NOT noninferior to prednisone. The upper limit of the CI for the absolute difference exceeded the preset 8% noninferiority upper limit.
- Patients, physicians and research assistants who assessed outcomes were all blinded to the intervention
- Randomization was adequately performed
- Baseline characteristics between groups were evenly matched
- The primary outcome is patient centered and clinically important
- Extensive exclusion criteria limits the applicability of these results to the general ED asthma population
- 20% of the study population was lost to follow up, which may have influenced results
- Using telephone follow up survey to assess primary and secondary outcomes is influenced by recall bias of the subjects, and limits the reassessment of the subject’s current condition without a physical examination
- A single center study limits generalizability to other settings
- Oral prednisone has a bitter taste and patients may have been unintentionally unblinded to treatment arm as a result
“A single dose of oral dexamethasone did not demonstrate noninferiority to prednisone for 5 days by a very small margin for treatment of adults with mild to moderate asthma exacerbations. Enhanced compliance and convenience may support the use of dexamethasone regardless”
The frequency of relapse was slightly higher with dexamethasone than prednisone (12.1% versus 9.8%),with an absolute difference was only 2.3%. Although this point estimate is below the preset upper limit for noninferiority, the upper limit of the confidence interval slightly exceeds the 8% difference set by the authors. As a result, this study does not establish noninferiority of single dose dexamethasone. However, due to issues of patient compliance with treatment regimens, a single dose of 12mg of dexamethasone by mouth seems like a reasonable alternative to a 5-day course of prednisone for adults with acute asthma exacerbations. A larger, multicenter trial investigating this intervention should be undertaken.
Potential Impact To Current Practice
The results of this study suggest that oral dexamethasone 12mg is either similar to or slightly inferior to a 5-day course of prednisone 60mg for adult patients with acute asthma exacerbations in the ED.
A single dose of oral dexamethasone 12mg may be a reasonable alternative to a 5-day course of prednisone 60mg for adults with asthma exacerbations.
National Asthma Education and Prevention Program. Guidelines for the Diagnosis and Management of Asthma. Expert Panel Report 3. Bethesda, MD: National Institutes of Health; 2007:1-404. Link