There are some things that we seem to do reflexively in the ED. Giving steroids to a patient with an asthma exacerbation is one of those things. Ask yourself the following question. Why do we do this? What is the evidence behind it? Can you cite any of the studies that lead to this common practice? I couldn’t fully elaborate on these – thus I’ve chosen it as the theme for this edition of WWDWWD.
How do they work?
Systemic glucocorticoids work just like the natural ones made in the adrenals (the kidney’s hat). They bind with glucocorticoid receptors- forming a complex, which then interacts with DNA to alter transcription of genes responsible for lots of stuff. In the case of asthma exacerbations this includes inflammatory mediators.
OK, prove it
Way back in 1993 (when I was a sophomore in high school) Scarfone et al demonstrated that children with a moderate asthma exacerbation who received prednisone as opposed to placebo had reduced risk of admission to the hospital. A meta-analysis from 2001 (when I was a second year med student) further supported the use of steroids in asthmatics. Rowe et al. noted that early ED administration within 1 hour of presentation was associated with reduced rate of admission. This meta analysis included a dozen RCT studies of almost 900 total patients. The pooled OR was 0.40, 95% CI: 0.21 to 0.78. The estimated number needed to treat is 8 95% CI 5-21. Children that didn’t get steroids before coming to the ED had a NNT of 7 and OR 0.37, 95% CI: 0.19 to 0.70. This probably means that these children were a bit sicker since they had already gotten steroids prior to their sentinel ED visit. Side effects were not significantly different between corticosteroid treatments and placebo.
Who should get them?
Basically, children with moderate exacerbations or worse. Children that have not received inhaled beta-agonists within a few hours of arrival to the ED and those that respond promptly and completely to a single dose do not benefit from steroids.
What is the usual dose & schedule for oral medications?
There are a few options:
- Prednisone/Prednisolone 1mg/kg orally – max 60mg/dose – once daily for 5 days (Fun-fact: Prednisone is metabolized into prednisolone in the liver)
- Dexamethasone 0.6mg/kg orally – max 10mg – once daily for one or two days
When should they be given?
ASAP – That much is clear. Zemek et al noted in their investigation of 644 children with asthma exacerbations that the administration of oral steroids by triage nurses reduced the odds of admission OR = 0.56; 95% CI: 0.36-0.87. Children ended up getting steroids 44 minutes earlier when they were administered in triage. Recall that steroids take at least 2-4 hours to start working – so this difference is important. As you’d expect, patents that got steroids in triage were better quicker – time to “mild” status median difference: 51 minutes; 95% CI: 17-84; P = .04. They were also discharged home faster – time to discharge median difference: 44 minutes; 95% CI: 17-68; P = .02. If your ED doesn’t do this you should be asking why.
Does it matter which one I administer?
Both oral prednisone and oral dexamethasone work great. This meta-analysis from Keeney et al. looked at 6 RCTs comparing the two aforementioned agents (single or 2-dose dexamethasone versus 5 days of prednisone) and noted the following:
- No difference in risk of relapse at 5 days RR 0.90, 95% CI 0.46-1.78 / 10-14 days RR 1.14, 95% CI 0.77-1.67 / or 30 days RR 1.20, 95% CI 0.03-56.93
- Patients who got dex vomited less often in the ED RR 0.29, 95% CI 0.12-0.69 / and at home RR 0.32, 95% CI 0.14-0.74.
Does the route of administration matter?
If the child can tolerate oral medicines – then give the steroids by mouth. Trust me, they will prefer that route. This is supported by the National Asthma Education and Prevention Program. There are no significant advantages to the IV route. You should consider giving the dose IM if they vomit the oral dose if you don’t need an IV for any other reason. This is supported by numerous studies, principally the following.
- Gries et al., 2000: The authors noted in this RCT that IM dexamethasone was associated with a similar improvement in clinical asthma score over the 5 days following the ED visit. Children were randomized to 5 days of 2/kg/day oral prednisone or 1x IM Dexamethasone. Additionally, there was no significant difference was seen in the rate of improvement between the 2 groups. Of note, many children in this study missed at least half of their oral steroid doses. There were no IM injectuon related complications. Nearly three out of four parents would choose IM again.
- Gordon et al, 2007: This study was a prospective, randomized trial in children aged 18 months to 7 years who presented to the ED with a moderate asthma exacerbation or worse. They were randomized to 1 dose of IM dexamethasone (0.6 mg/kg, max 15 mg) or oral prednisolone 2 mg/kg for 5 days. They found that there was no difference in clinical score at 4 days or rate of readmission by 2 weeks for either group.
Inhaled steroids for acute exacerbations is still being investigated. The data comparing oral versus inhaled is inconclusive at best.
Are there any downsides?
A short course of prednisone at 1-2mg/kg will not effect bone density, height, or adrenal function at 30 days. There may be transient, clinically insignificant impact of bone deposition and adrenal function however. There doesn’t seem to be a conclusive increases in nausea, tremor, and headache when compared with placebo. Studies have shown that kids getting 2mg/kg/day had more behavioral side effects than 1mg/kg/day. See Kayani et al. for more.
Please, keep administering systemic corticosteroids for children with moderate exacerbations of asthma. You can choose either 1mg/kg (max 60mg) of PO prednisone/prednisolone for 5 days or 1-2 days of dexamathasone 0.6mg/kg (max 10mg). If the PO route isn’t gonna happen, consider going IM if you don’t need the IV for anything else (like fluids or Magnesium). And finally, get them into the patient ASAP as it will increase the speed of their clinical improvement and decrease their time in dpeartment