Single Dose Dexamethasone or 5 Days of Prednisone in Adult Asthmatics?

11 Aug
August 11, 2016

Single Dose DexamethasoneBackground: 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.

Article:

  • Rehrer MW et al. A randomized controlled noninferiority trial of single dose of oral dexamethasone versus 5 days of oral prednisone in acute adult asthma. Ann Emerg Med 2016. PMID: 27117874

Clinical Question:

  • 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?

Population:

  • 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.

Intervention:

  • 12mg of oral dexamethasone in the ED plus 4 days of placebo capsules 

Control:

  • Prednisone 60mg in ED plus 4 days of 60mg of prednisone

Outcomes:

  • Relapse, as 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

Design:

  • Prospective, randomized, triple-blinded, controlled, noninferiority single center trial 

Excluded:

  • 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
  • Severe exacerbations requiring immediate airway intervention such as noninvasive bilevel airway support or intubation
  • Those admitted to the hospital
  • Patients with a history of chronic obstructive respiratory disease, pulmonary fibrosis, HIV/AIDS, congestive heart failure, active varicella, active tuberculosis, or diabetes mellitus

Primary Results:

  • 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.

Clinical Findings:

  • 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 isn’t non-inferior (Not Non-inferior = Sacrifice small amount of benefit for simpler dosing schedule) to prednisone. The upper limit of the CI for the absolute difference exceeded the preset 8% noninferiority upper limit.

Strengths:

  • 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

Limitations:

  • 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

Author’s Conclusions: “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”

Our Conclusions: 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.

Clinical Bottom Line: 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.

References:

  1. 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

Guest Post By:

Alli Boyd, MD

Post Peer Reviewed By: Salim R. Rezaie (Twitter: @srrezaie)

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Anand Swaminathan

Clinical Assistant Professor of Emergency Medicine at Bellvue/NYU
REBEL EM Associate Editor and Author

Latest posts by Anand Swaminathan (see all)

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1 reply
  1. Eric says:

    Tell you what: I’ll give a dose of dexamethasone in ED and an Rx for Prednisone. Ought to give everyone best outcome…

    Reply

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