Author: Jim Kenny, MD (EM Resident Physician, PGY-3, NUEM) // Edited by: Joshua Zimmerman, MD (EM Resident Physician, PGY-4, NUEM) // Expert Commentary: Zachary Pittsenbarger, MD
Citation: [Peer-Reviewed, Web Publication] Kenny J, Zimmerman J (2016, August 9). Steroid Selection In Pediatric Asthma [NUEM Blog. Expert Commentary by Pittsenbarger Z]. Retrieved from http://www.nuemblog.com/blog/steroids-in-pediatric-asthma/
Introduction
As many of us know, pediatric asthma exacerbations account for a significant portion of trips to the emergency department (ED), comprising 2-4.5% of ED visits each year. As a common disease of the pediatric population, effective ED management minimizes the financial cost, missed school days and emotional costs to the patient and their family. The current mainstay of treatment is beta-agonist and corticosteroid administration. In order for this regimen to be effective, compliance is key.
Steroids In Asthma
Prednisone and prednisolone are the two most commonly used corticosteroids for pediatric asthma exacerbations. The most common dosing regimen is 1-2mg/kg (max dose 60mg) PO once-to-twice daily for 3-5 days. Given the potential for multiple doses per day for multiple days, some clinicians have questioned whether an equivalent dose of dexamethasone is just as efficacious. Dexamethasone’s half-life is double that of each medication (12-36 hours for prednisone/prednisolone vs 36-72 hours for dexamethasone) and thus, a single dose may provide an equipotent therapy compared to multiple doses of either other steroid. In addition, the greatest benefit of corticosteroids in asthma exacerbations is thought to be during the first 3 days, allowing dexamethasone to be used as a one time dose. The most commonly studied formulations for this situation are 0.3-0.6 mg/kg/day (max 16mg) for 1-2 doses. Similar doses of dexamethasone have been used in pediatric patients with croup and bacterial meningitis, making it seemingly safe for asthma exacerbations as well.
Non Inferiority
There have been several randomized controlled trials (RCTs) that have studied dexamethasone vs. prednisone/prednisolone in pediatric asthmatic patients and the overarching message is that dexamethasone is non-inferior in the treatment of pediatric asthma exacerbations. Dexamethasone has demonstrated no statistically significant difference in relapse rates (defined as return visit to ED, clinic, or unanticipated hospitalization in one meta-analyses of 6 RCTs) and has demonstrated a lower frequency of emesis. Multiple studies have also demonstrated noncompliance with prednisone and some literature suggests that parents would prefer the one time dexamethasone to prednisone. This, along with the decreased dosing requirements and potential for improved palatability, make dexamethasone an attractive alternative to prednisolone in this patient population, particularly with regard to cases where compliance is a concern.
Limitations
The main limitation of the current literature is that there is a disagreement between studies regarding the ideal dose. The question still remains is 0.3 mg/kg or 0.6 mg/kg the ideal dose and whether a single, or two dose, regimen is needed. Moreover, 3 of the studies used intramuscular (IM) formulations of dexamethasone as opposed to oral regimens, one using a dose as high as 1.7mg/kg IM. Most of the studies also excluded patients with a high fever, other signs of infection such as active herpes/varicella, tuberculosis exposure and critically ill asthma exacerbations (in which case intravenous corticosteroids is preferred). Therefore, this data is most applicable to those patients that you feel are likely to be discharged home or potentially admitted to a non-ICU setting.
Conclusion
Nevertheless sufficient evidence exists to suggest using dexamethasone for immunocompetent pediatric asthma patients who may be discharged home or admitted in a non-ICU setting. The current literature suggests that IM and PO are equally efficacious, so a conservative approach with 0.6mg/kg PO or IM initially and then a second dose PO, would likely be acceptable to most practicing emergency physicians and would have the added benefit of still dispensing a single, potentially therapeutic dose in the ED in the event the second dose is not taken. Two doses would also address the main statistically significant difference between the two groups in the most recent article from Cronin et al. which demonstrated that the dexamethasone group was more likely to require repeat doses of corticosteroids. Further RCTs with comparison to existing literature are necessary to definitively determine which dosing regimen is most appropriate.
Expert Commentary
Hi Jim,
That was a nice review of the recent literature. We know steroids given early in the illness improve outcomes for patients. But when it comes to writing the order for the medication, the devil is in the details. Which med? What dose? How long to treat? We face decisions on which medication, how much of it, how often to give it, and how long to give it for. This takes the reflexively simple choice to give steroids and changes it in to a complicated mess of uncertainty.
The first decision point clearly is which corticosteroid to give, as this dictates much of the treatment course. If dexamethasone, particularly in one dose, is as effective as prednisolone (without more side effects) then many of those questions above are obviated. The meta-analysis by Keeney, et al. is helpful to interpret the data of several smaller studies which were not powered appropriately to look at the question of dexamethasone as a superior, or at least non-inferior, option to prednisone/prednisolone. They conclude there is no difference in treatment failures between the two medications. Also, the paper highlights the secondary outcome that dexamethasone treated patients vomited less. Regarding the question of less emesis, the cynic in me also notes that patients were included that received an IM injection of dexamethasone. It seems very expected that an IM injection would cause less emesis than a PO medication. Of note, they didn’t look at the difference in injection site pain between the PO and IM routes, but I would be confident that PO prednisone would be favorable to IM dexamethasone there.
Very recently (May of 2016) the Cochran Library updated their meta-analysis titled “Different Oral Corticosteroid Regimens for Acute Asthma.” They analyzed the same questions with largely the same set of studies with two other data sources that are only now available. However, they conclude that the data is too weak to draw any conclusions secondary to study heterogeneity and possible biases. The authors there determined, that they could not reject the null hypothesis.
Where does that leave us with two conflicting results from the same data set? Perhaps, the real take away message should be that any difference between different corticosteroids is likely negligible. They have looked at thousands of patients, and any clinically important difference should have been determined by this point. This will lead some people to continue the status quo and use prednisone and prednisolone. Others may decide that dexamethasone with fewer doses is more ideal for patients. But in reality, many patients will have variations in their stories that may drive you to one medication or the other: “My child did not sleep for days after he had dexamethasone for croup.” Prednisolone for you. “My daughter is a terror taking medications and spits out every dose I give her at home.” Let’s try dexamethasone. Having options is nice.
Zachary Pittsenbarger, MD FAAP
Instructor, Division of Emergency Medicine, Department of Pediatrics, Feinberg School of Medicine, Northwestern University
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References
- Keeney GE, Gray MP, Morrison AK, et al. Dexamethasone for acute asthma exacerbations in children: a meta-analysis. Pediatrics. 2014;133:493-499.
- Redman E, Powell C. Prednisolone or dexamethasone for acute exacerbations of asthma: do they have similar efficacy in the management of exacerbations of childhood asthma? Arch Dis Child. 2013;98:916-919.
- Schwarz, Evan S, et al. Is Dexamethasone as Effective as Prednisone or Prednisolone in the Management of Pediatric Asthma Exacerbations? Ann Emerg Med. 2014;65:81-82.
- Shefrin AE, Goldman RD. Use of dexamethasone and prednisone in acute asthma exacerbations in pediatric patients. Can Fam Physician. 2009;55:704-706.
- Cross KP, Paul RI, Goldman RD. Single-dose dexamethasone for mild-to-moderate asthma exacerbations: Effective, easy, and acceptable. Can Fam Physician. 2011;57:1134-1136.
- Cronin J, et al. A Randomized Trial of Single-Dose Oral Dexamethasone Versus Multidose Prednisolone for Acute Exacerbations of Asthma in Children Who Attend the Emergency Department. Ann Emerg Med. 2016;67:593 – 601.
- Linzer JF. Asthma. In: Wolfson AB, ed. Harwood-Nuss’ Clinical Practice of Emergency Medicine. 6th ed. Philadelphia, PA: Wolters Kluwer; 2015:1224-1230.
- Normansell R, Kew KM, Mansour G. Different oral corticosteroid regimens for acute asthma. Cochrane Database Syst Rev. 2016;5:CD011801.