Evidence Based Strategies for Common Clinical Questions

Dexamethasone: An Effective and Equitable Choice for Asthma Exacerbations

Author: Claire Seguin, MD | Pediatric Hospital Medicine Fellow

Column Editor: Kathleen Berg, MD | Co-Director, Department of Evidence Based Practice | Pediatric Hospitalist, Division of Pediatric Hospital Medicine | Associate Professor of Pediatrics, UMKC School of Medicine 

Believe it or not, springtime is coming. And with it will come pollen, and asthma exacerbations. Systemic steroid administration during moderate and severe exacerbations has been a Grade A recommendation by the National Heart, Lung, and Blood Institute’s NHLBI Expert Panel Report Guidelines on Asthma from its earliest iterations in the 1990s to its most recent in 2020.¹ Prednisone (tablets) and prednisolone (liquid) daily for three to five days have been most widely used; however, dexamethasone (tablet and liquid) has been used with increasing frequency because of its useful pharmacokinetics. While the anti-inflammatory effects of prednisone/prednisolone last 18-26 hours, dexamethasone’s effects exceed 48 hours.² This duration makes it a useful option for the patient or family when administering a daily steroid medication is a challenge. Although it might be ideal to provide a one-time dose of dexamethasone to mitigate the risk of noncompliance, we must ask whether dexamethasone is as effective as prednisone/prednisolone at reducing recurrence of asthma exacerbations in children.

This question has been the focus of recent medical research. Four studies, including two systematic reviews,^3,4 a randomized controlled trial,⁵ and a cohort study⁶ comparing one dose of dexamethasone to three to five days of prednisolone found no differences in risk of symptom relapse. Studies comparing two doses of dexamethasone to five to six days of prednisolone similarly did not find differences in risk of relapse.^4,7,8 Finally, a retrospective cohort study comparing prednisolone and dexamethasone both before (one to three doses of each), and after (two doses of dexamethasone vs. five doses of prednisolone) arriving at the hospital found no differences in length of stay between the steroid groups for either course.⁹ To date, studies addressing this question are characterized by some uncertainty due to low number of subjects, infrequent readmission events, and/or risk of biases. Only three of these studies reported race or ethnicity of participants. In addition, variations in dosing and definitions of symptoms pose challenges to their generalizability. Large, double blinded randomized controlled trials are needed to answer with more certainty the question of whether dexamethasone is equally as effective as prednisolone in reducing symptom recurrence.

In the meantime, clinicians should consider other factors when choosing a systemic steroid for their patient. These should include side-effect profiles, tolerability, frequency of dosing, and costs (both direct and indirect) to the family. The studies that evaluated the side effect of gastrointestinal upset as a secondary measure found that dexamethasone was tolerated equally to prednisone/prednisolone.^5,7 While some previous formulations of dexamethasone had been unpalatable, many children tolerate the newer formulations well. Further, for children who will not happily take medication, less frequent dosing can lead to a meaningful reduction in stress for children and their families.

Direct and indirect costs are important to consider when prescribing any medication to a patient. While exact monetary costs to the family vary based on type of medical insurance (if any), a rough comparison of local per-dose pricing shows a five-day course of prednisolone costs $18 to $48, while a one- to two-dose course of dexamethasone costs $11 to $32. Volk et al. identified similar cost differences in their study.⁸ An additional indirect cost to consider is the cost to families of travel to a pharmacy, which may involve transportation, child care, and time away from work. While this cost may be unavoidable if dexamethasone is prescribed in a clinic setting, providing only one dose in an acute care or inpatient setting eliminates the need for a prescription. If a two-dose course is preferred by the provider, the family would still have an additional one to two days to obtain the second dose of dexamethasone, allowing the family to coordinate for this unexpected expenditure of time and money.

Based on the available evidence, dexamethasone and prednisolone are equally efficacious when taken appropriately. Providers should make their choice based on the specific circumstances of their patient and the patient’s family, keeping in mind that the need for a prescription and more frequent dosing may be more difficult for those facing challenges with health literacy, transportation or insurance coverage. Dexamethasone is easier to administer and less expensive, potentially reducing the risk of noncompliance or health care inequities. As asthma flares this spring, providers can be reassured that they have two good options in their toolbox for management of exacerbations.

References:

1. Cloutier MM, Baptist AP, Blake KV, et al; Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC). 2020 focused updates to the asthma management guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020;146(6):1217-1270. doi:10.1016/j.jaci.2020.10.003
2. Dexamethasone. Lexi-Drugs. Lexicomp Online. Lexicomp; 2022. Accessed March 1, 2022. http://online.lexi.com
3. Kirkland SW, Cross E, Campbell S, Villa-Roel C, Rowe BH. Intramuscular versus oral corticosteroids to reduce relapses following discharge from the emergency department for acute asthma. Cochrane Database Syst Rev. 2018;6(6):Cd012629. doi:10.1002/14651858.CD012629.pub2
4. Normansell R, Kew KM, Mansour G. Different oral corticosteroid regimens for acute asthma. Cochrane Database Syst Rev. 2016;(5):Cd011801. doi:10.1002/14651858.CD011801.pub2
5. Elkharwili DA, Ibrahim OM, Elazab GA, Elrifaey SM. Two regimens of dexamethasone versus prednisolone for acute exacerbations in asthmatic Egyptian children. Eur J Hosp Pharm. 2020;27(3):151-156. doi:10.1136/ejhpharm-2018-001707
6. Watnick CS, Fabbri D, Arnold DH. Single-dose oral dexamethasone is effective in preventing relapse after acute asthma exacerbations. Ann Allergy Asthma Immunol. 2016;116(2):171-172. doi:10.1016/j.anai.2015.11.015
7. Paniagua N, Lopez R, Muñoz N, et al. J Pediatr. 2017;191:190-196.e191. doi:10.1016/j.jpeds.2017.08.030
8. Volk AS, Marton SA, Richardson BS, Rauda L, Schwarzwald HL, Naik NM. Oral dexamethasone to control wheezing in children at an outpatient clinic. Clin Pediatr (Phila). 2019;58(2):151-158. doi:10.1177/0009922818809466
9. Hemani SA, Glover B, Ball S, et al. Dexamethasone versus prednisone in children hospitalized for acute asthma exacerbations. Hosp Pediatr. 2021;11(11):1263-1272. doi:10.1542/hpeds.2020-004788