Podcast #24 - Single Dose Dexamethasone in Adult Asthma

Dexamethasone (the chemical demonstrated here) is commonly used in the treatment of asthma exacerbations both in adults and children. It is growing popularity with new research that supports its role over traditional alternatives such as prednisone. One key difference is its longer lasting effect. However, this new paper demonstrates some potential limitations as discussed in this review.

​Title: A Randomized Controlled Noninferiority Trial of Single Dose of Oral Dexamethasone Versus 5 Days of Oral Prednisone in Acute Adult Asthma
 
Case: A 24 y/o non-pregnant female comes to your department complaining of wheezing and says she used to have an albuterol inhaler but it ran out and she does not have a new prescription. She was treated with two albuterol treatments in the department with significant improvement.  You plan to discharge her home with a prescription for an albuterol inhaler and a steroid.  In the past she has taken a five day course of prednisone with relief of symptoms, but she says she often forgets to take the pills on the last couple of days and is asking for an alternative, especially one she could take in the department as an alternative.
 
Background: Acute asthma exacerbations account for more than 2.1 million Emergency Department (ED) visits annually and in the US effects 8.4% of the population. 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 has similar bioavailability, with the duration of action of 72 hours. Previous studies for pediatric asthma have been promising for dexamethasone as an alternative to other treatments andthere has also been promise with a 2-dose regimen in adults.  The thought is that with simple dosing of dexamethasone versus multi-day dosing of routine medications such as prednisone there will be a decrease in the rate of relapse if a single dose medication was used and given in the ED.  
 
Clinical Question: Is a single dose of 12mg of oral dexamethasone not inferior to 5 days of oral prednisone in the treatment of adults with mild to moderate asthma exacerbation in preventing relapse?
 
Reference:

• Population: Patients aged 18-55 years old with a history of asthma presenting to the ED with an acute episode of asthma requiring more than 1 albuterol nebulizer treatment, and were discharged home with a valid telephone number for follow-up.      
  • Exclusion Criteria: Patients less than 18 years old or over 55 years old (the older age limit to help reduce concurrent COPD), those without a working telephone number (for follow-up purposes), pregnant patients, previous allergic reaction to steroids, reported use of oral steroids two weeks before presentation, history of chronic respiratory disease such as COPD or pulmonary fibrosis, HIV/AIDS, congestive heart failure, active varicella, active tuberculosis, asthma requiring immediate airway intervention such as noninvasive bilevel airway support or intubation, and those admitted to the hospital.
• Intervention: 12mg of oral dexamethasone plus 4 days of placebo. 
• Comparison: 60mg of oral prednisone for 5 days.
• Outcome: Relapse which was defined as an unscheduled return visit to a healthcare provider for additional treatment for persistent or worsening asthma within 14 days.

 
Author’s Conclusions: A single dose of oral dexamethasone did not demonstrate noninferiority (meaning it was inferior) to prednisone for 5 days by a very small margin for treatment of adults with mild to moderate asthma exacerbation.  Enhanced compliance and convenience may support the use of dexamethasone regardless.
 
Quality Checklist for Randomized Clinical Trials:

1. The study population included or focused on those in the ED. Yes
2. The patients were adequately randomized. Yes
3. The randomization process was concealed. Yes
4. The patients were analyzed in the groups to which they were randomized. Yes
5. The study patients were recruited consecutively (i.e. no selection bias). Yes
6. The patients in both groups were similar with respect to prognostic factors. No, there were some differences between the two groups
7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Yes
8. All groups were treated equally except for the intervention. No, there were some differences such as prescriptions on discharge
9. Follow-up was complete (i.e. at least 80% for both groups). No, there was a large loss to follow-up in the dexamethasone group
10. All patient-important outcomes were considered. Yes
11. The treatment effect was large enough and precise enough to be clinically significant. No

 
Key Results: 173 patients receiving dexamethasone and 203 receiving prednisone completed the study regimen and telephone follow-up.  The dexamethasone group by a small margin surpassed the present 8% difference between groups for noninferiority in relapse rates within 14 days (12.1% versus 9.8%; absolute difference of 2.3%; 95% confidence interval -4.1% to 8.6%).  Subjects in the 2 groups had similar rates of hospitalization for their relapse visit (dexamethasone 3.4% versus prednisone 2.9%; absolute difference 0.5%; 95% confidence interval -4.1% to 3.1%).  Adverse effect rates were generally the same in the 2 groups.
 
Key Points of Debate:

• People only enrolled if received multiple breathing treatments
  • May have missed some patients who could still have been candidates.
  • Many who come to the ED with asthma exacerbation will still receive a steroid even if only one treatment given.
  • Others may have been missed because patients could have refused to receive multiple treatments.
• Some patients could have qualified because of age but may still have COPD even though they tried to exclude based on age
  • Some people may not have been treated effectively given the confounder of COPD. 
  • There is also the concern for other pulmonary diseases that may not yet have been diagnosed or misdiagnosed as asthma.
• There were potential differences in prognostic factors and how the two groups were treated differently.
  • Example being inhalers prescribed.
  • Almost twice as many patients in the prednisone group (54 versus 30) received a prescription of inhaled steroids on discharge.
• A significant number of people in the dexamethasone group were lost to follow-up.
  • Approximately 24% of the dexamethasone group was lost on follow-up and approximately 15% for prednisone.
  • Led to an almost 20% loss of follow-up total.
  • Limits the validity of the study and its results.
• Additionally, telephone follow-up carries a risk of bias.
  • Recall bias influences the results of the study as people then answer questions later by telephone.
  • This also limits the ability to reassess the patient and their current condition without a physical examination.
• Study may have limited value as single-center and with the way prescribed
  • Multi-center would have been better as single-center studies limit the ability to generalize results.
  • Also worth mentioning that all of the medications were given (placebo or remainder of prednisone packet) in the department.
  • Even then, 8.7% of the prednisone arm did not finish their medication whereas previous studies demonstrate up to 20% of people do not fill their prescription.  Adherence at 7 days in one study found it was only 50%.
  • A single dose of a medication would eliminate prescription adherence barriers previously demonstrated such as forgetfulness, cost, and dose omission.
  • This is a key point as most places will not provide five days of medication free and apparently if they did would still not have perfect compliance.
  • When talking about single dose alternatives, there could be alternatives such as an intramuscular combination injection of dexamethasone 10mg and methylprednisolone acetate 80mg.

 
Comparing Conclusions:
The study is unfortunately limited due to a number of limitations and the considerable loss of follow-up.  This negative study is by no means conclusive but does hold some potential to the applications of dexamethasone in this population.
 
Our Bottom Line:
We agree that this study did not demonstrate a single dose of oral dexamethasone to be noninferior to prednisone for 5 days by a very small margin.  However, there is still potential for dexamethasone in the treatment of adults with mild to moderate asthma exacerbation.  Further studies with fewer limitations and better compliance are needed though to help confirm this hypothesis.
 
Case Resolution:
You have a detailed discussion with your patient on the risks and benefits of using dexamethasone versus prednisone.  With shared decision making, you discuss how a single dose of dexamethasone may not be enough and that other options such as a two day course of dexamethasone or the five day course of prednisone could be used amongst other options.  After careful review, your patient elects to go with the two day option as she feels she can remember to take one more dose at home.  After a dose is dispensed here and prescriptions provided, you review your standard return precautions and the patient does well at home. 
 
Clinical Application:
At this time, the data is very limited in adults for a single dose of dexamethasone.  However, two doses of dexamethasone have been shown to be helpful versus five days of prednisone.  Until further research can be obtained, alternatives should be considered first before using this option and only after a careful discussion with the patient regarding single-dose dexamethasone.
 
What do I tell my patient?
You are having an asthma exacerbation and an important part to treating this is using steroids.  We can often give this orally with multiple doses.  A new study tried to do a single dose of a steroid known as dexamethasone but was not able to show it was as effective as five days of prednisone.  For best effect we can try two days of the dexamethasone of five days of the prednisone.  If you feel this will not work we can discuss our options further on the single dose of dexamethasone. 
 
Conclusion:
Thank you for listening to the podcast and reading the blog.  Please let me know if there is anything we need to change or improve.  Please remember to help promote us visiting us at Libsyn, sharing on Facebook, retweeting on Twitter, and rating on iTunes to help spread the word on TOTAL EM.  If you have any questions you can comment below, email at thetotalem@gmail.com, or send a message from the page.  We hope to talk to everyone again soon.  ​Until then, continue to provide total care everywhere.

podcast_24.mp3
File Size:	12621 kb
File Type:	mp3

Download File

---