Kids with Asthma? Reach for Dexamethasone

A one-time dose of dexamethasone in the ED might be superior to current pediatric asthma management. Check the research. 

You are working a moderately busy evening shift in the pediatric ED. The medical student has just finished presenting the kid he saw in bed 8. The patient is an 8-year-old boy with known asthma, here with an acute exacerbation in the setting of a mild upper respiratory infection. Based on his asthma severity score he is likely to go home but he is currently wheezing and needs treatment. The student proposes inhaled albuterol and atrovent, which sounds like a good plan. Then the conversation turns to steroids. The student wants to order a dose of prednisolone in the ED and then send the patient home with 4 more days of prednisolone to complete a 5-day course. It is what he has seen his preceptors do on other occasions. You suggest a single dose of dexamethasone instead. The student wants to know what evidence supports this therapy and why you are choosing this approach.

In your US emergency practice, the common treatment for mild-moderate asthma is 2 mg/kg of prednisone/prednisolone orally in the acute setting, followed by 4 additional days of 1mg/kg twice daily. This does not always go as planned, however. In 2001, Cooper and Hickson published a retrospective cohort study of 6,035 Tennessee Medicaid patients aged 2 to 17 years either seen in the ED or admitted to the hospital with asthma [^1]. These patients were then sent home with prescriptions for prednisone/prednisolone. The study found that only 44.8% of the children discharged from the ED filled the prescription within 7 days and only 55.5% of the children discharged from the hospital filled it within 7 days. This is not the only argument against prednisone/prednisolone. Patients frequently complain about the bitter taste of the drug and will sometimes experience vomiting after taking it.

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Dexamethasone is 5-6 times more potent than prednisone/prednisolone. It is more palatable and is associated with less vomiting. The half life of predisone/prednisolone is 12-36 hours while the half life of dexamethasone is 36-72 hours [^2]. But prednisone/prednisolone has been the standard therapy for many years. What is the evidence that dexamethasone is as effective?

In 1997, Jean Klig and colleagues published a small, randomized clinical trial involving 42 ED patients, ages 3-16 years with asthma, who were well enough to be discharged home [^3]. They compared a single dose of 0.3 mg/kg IM dexamethasone versus 2mg/kg of oral prednisone for 3 days. Patients were followed up after 5 days either in clinic or by telephone. All of the patients had clinical improvement in their asthma symptoms and there were no hospitalizations. Based on this pilot study, the authors concluded that a single dose of IM dexamethasone given in the ED produced results similar to 3 days of prednisone.

In 2000, Gries and colleagues published another small randomized clinical trial of dexamethasone versus oral prednisone [^4]. This was done in a clinic setting with children aged 6 months to 7 years. 16 patients were randomized to receive a single dose of 0.4 mg/kg of dexamethsone and 17 patients were randomized to receive to receive 5 days of 2m/kg oral prednisone. Families kept a symptom diary and patients were reassessed in clinic. All patients improved in 5 days and there was no difference between groups.

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These were both small studies. In 2007, Gordon and colleagues published a larger randomized clinical trial of IM dexamethasone versus oral prednisolone [^5]. Patients were 18 months to 7 years old with asthma in an ED setting. 88 were treated with 0.6 mg/kg IM dexamethasone as a single dose and 93 were treated with 2mg/kg of oral prednisolone for 5 days. Patients were reassessed 4 days later using an asthma severity score. Again, there was no significant difference between the two groups.

At this point the medical student does not appear convinced. After all, two of these studies had pretty small numbers. Shots hurt and children and their parents are well aware of that. Besides, two of those studies you cited included children less than 2 years of age. A lot of clinicians are uncomfortable diagnosing asthma that young. What if they had bronchiolitis instead? That doesn’t respond to steroids. Wouldn’t that bias your hypothesis toward the null, that is, no difference between groups?

You concede the student’s points. However, there are three additional randomized clinical trials that have looked at oral dexamethasone, not IM. None of them included children less than 2 years of age. What have those studies shown?

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In 2001, Qureshi and others published a randomized clinical trial of 2-18 year olds with asthma in an ED setting [^6]. The purpose was to compare two days of oral dexamethasone dosed as 0.6 mg/kg with 5 days of oral predisone/prednisolone dosed as 2mg/kg in the ED, then 1mg/kg/day for 4 days. 272 children were analyzed in the dexamethasone group and 261 in the predisone/prednisolone group. There was no significant difference between the groups in relapse rates, hospitalization rate or symptom persistence. The group receiving predisone/prednisolone had more vomiting in the ED, more noncompliance with medication and missed more days of school.

In 2006, Altamimi and others published another prospective, randomized trial in an ED setting [^7]. In this study of children aged 2-16 years, 56 were given one dose of oral dexamethasone of 0.6 mg/kg and 54 were given 5 days of oral predisone/prednisolone at 2 mg/kg/day. They were evaluated by phone 48 hours after leaving the ED, and then had a revisit at 5 days post discharge. The primary outcome was return of self-assessment score to baseline. There was no significant difference between the two groups. In 2008, Greenberg and colleagues published another randomized clinical trial in an ED setting [^8]. They looked at 38 2-18 year olds who got a five-day course of 2mg/kg of oral prednisone compared with 51 who got a two-day course of oral 0.6 mg/kg dexamethasone. The follow-up medications were given in blister packs to ensure compliance. The outcomes of interest were relapse within 10 days or vomiting in the ED. There was no significant difference between the two groups.

The most recent randomized clinical trial to address the question of oral dexamethasone versus predisone/prednisolone was published by Cronin and colleagues in 2016 [^9]. This was done in an ED setting in Ireland and involved children aged 2-16 years. 245 patients were analyzed. The dosing schedule was different from the prior studies of oral dexamethasone. The dose of dexamethasone was 0.3 mg/kg, which is half of what was given in the other trials and the dose of prednisolone was 1 mg/kg, again half of the dose in the other trials. The dexamethasone was given as a single dose in the ED and the prednisolone was given over 3 days, as opposed to 5 days in the other trials. The primary outcome was asthma scores on day 4 which were no different between the two groups. Hospitalizations rates and unscheduled return visits were also not different. 14 children vomited with the prednisolone versus none of the dexamethasone patients.

The student looks convinced. You probably had him when you quoted the rate of unfilled prescriptions but you definitely won him over when you told him it could be given as a single oral dose in the ED. Some caution is needed, however. Although there are currently six randomized trials showing dexamethasone to be just as good as predisone/prednisolone, three gave the dexamethasone IM, one gave two days of oral dexamethasone and only two gave a single ED dose. Of those two, one was small and the other used lower doses than are standard in the US. So the verdict is probably still out for now. But it is an option worth considering. Based on the dose used in four of the six trials reviewed, you order 0.6 mg/kg of oral dexamethasone (maximum 15-18 mg) and move on to the next patient.

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REFERENCES

1. Cooper WO, Hickson GB. Corticosteroid prescription filling for children covered by Medicaid following an emergency department visit or a hospitalization for asthma. Arch Pediatr Adolesc Med. 2001;155:1111-1115.
2. Schimmer BP, Parker K. Goodman and Gilman’s The pharmacological basis of therapeutics. Adrenocorticotropic hormone, adrenocortical steroids and their synthetic analogues, inhibitors of the synthesis and actions of adrenocortical hormones. 11th edition. Edited by Bruton L, Lazo J, Parker K. Columbus, Ohio: The McGraw-Hill Companies, Inc. 2006.
3. Klig JE, Hodge D, Rutherford MW. Symptomatic improvement following emergency department management of asthma: a pilot study of intramuscular dexamethasone versus oral prednisone. Journal of Asthma. 1997:34 (5);419-45.
4. Gries DM, Moffitt DR, Pulos E, Carter ER. A single dose of intramuscularly administered dexamethasone acetate is as effective as oral prednisone o treat asthma exacerbations in young children. J Pediatr 2000;136:298-303.
5. Gordon S, Tompkins T, Dayan PS. Randomized trial of single-dose intramuscular dexamethasone compared with prednisolone for children with acute asthma. Pediatr Emerg Care. 2007;23(8):521-527.
6. Qureshi F, Zaritsky A, Poirier MP. Comparative efficacy of oral dexamethasone versus oral prednisone in acute pediatric asthma. J Pediatr. 2001;139:20-26.
7. Altamimi S, Robertson G, Jastaniah W, et al. Single-dose oral dexamethasone in the emergency management of children wih exacerbations of mild to moderate asthma. Pediatr Emerg Care. 2006;22(12):786-793.
8. Greenberg RA, Kerby G, Roosevelt GE. A comparison of oral dexamethsaone with oral predisone in pediatric asthma exacerbations treated in the emergency department. Clin Pediatr. 2008;47(8):817-823.
9. Cronin JJ, McCoy S, Kennedy U, 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 of Emerg Med. 2016;67(5):593-601.