One-time Dex is a reasonable choice for patients unlikely to fill a prescription.
We’ve all seen that asthma patient bounce back, a few days later. I’ve usually attributed it to a tough home environment, or workplace triggers, or maybe just severe underlying disease. A few patients were probably non-adherent to steroids, I figured—but only a few.
Then I read Amy Levine’s article in EPMonthly last month. She cited a 2001 paper from Cooper & Hickson that only 45% of Tennessee pediatric asthma patients discharged from an ED had their predisone or prednisolone prescriptions filled within seven days. This was much higher than I had anticipated, and while I haven’t found a study on adults, it wouldn’t surprise me if their non-adherence was worse.
Levine went on to review the pediatric literature—many small studies and a few larger randomized trials—to conclude that a single dose of dexamethasone was probably as good as a course of prednisone for kids in the ED with asthma exacerbations. Unfortunately, the doses and routes of administration were not the same across all trials, though 0.6 mg/kg IM dexamethasone was the most common and seems as effective as prednisone.
What’s the situation for adults? As luck would have it, Rehrer and colleagues just published a study in Annals of EM, on the topic of dexamethasone vs prednisone in ED management of adults with asthma exacerbations. In this single-center (in Oakland, CA) triple-blinded trial, adults aged 18-55 were randomized to receive either 12 mg of dexamethasone PO in the ED (plus 4 days of placebo capsules) or 60mg of prednisone in the ED (plus another 4 days outpatient). The outcome they looked at was unscheduled return visit to a healthcare provider with persistent or worsening asthma symptoms. They measured this outcome via telephone follow-up at two weeks.
Their exclusion criteria were reasonable. They randomized 465 patients, but several in both arms were admitted or later excluded, and a high number (20%) were lost to follow-up. Though randomized, each group had similar baseline characteristics: average age of 32, averaging three days of symptoms, similar vitals, and peak flows. About 10% of each group had been in the ED in the past month.
They found the two-week relapse rate with dexamethasone was 12.1%, compared to 9.8% for prednisone. Was this 2.3% difference real or just noise? Was dexamethasone about same as prednisone, or actually worse? Well, it gets complicated. This was a non-inferiority trial, which means our classic “null hypothesis” isn’t null at all, and the study is attempting to show whether a new treatment is significantly worse than the old by a pre-determined “non-inferiority margin.”
Rehrer’s group had designed this study so that non-inferiority of dexamethasone would be satisfactorily demonstrated, if the upper limit of the confidence interval fell below 8%. This didn’t happen. The 2.3% difference between dex and prednisone had a confidence interval that reached up to 8.6%.
But that didn’t stop the authors from concluding that, while non-inferiority wasn’t demonstrated, it was very close, and “enhanced compliance and convenience may support the use of dexamethasone regardless.”
Michael Carson wrote a letter to the editor, lamenting that the authors were allowed to communicate these qualifiers and recommendations, despite the fact the study didn’t show what it was designed to show.
The editors doubled down, standing by the research, analysis, and authors statements, concluding that “single dose of oral dexamethasone 12 mg is either similar to or slightly inferior to a 5-day course of prednisone 60 mg for asthma.”
I agree with the editors (and authors) here. This study, by itself, tells me that if I had a patient who was really at risk for not filling their steroid prescription, dexamethasone is a reasonable alternative.
And this study isn’t the only one to examine the issue. Aboeed in 2014 compared 40mg of prednisone for five days versus 16 mg of dexamethasone for two days (revisit rates were similar in both groups). Others have looked at other regimens. A Cochrane review last year found insufficient evidence to suggest superiority, or equivalence, between one steroid and other—with revisits, admissions and serious adverse events being too infrequent to draw any firm conclusions.
The way I look at it is this: The major difference between dex and prednisone is the half-life (36-72 hours for dexamethasone vs 12-36 for prednisone) and its lack of mineralocorticoid effect. The original studies of dexamethasone in asthma read somewhat comically, compared to today’s research (In 1959, Slater wrote things like, “the disastrous results obtained in the first two cases showed us this dose was totally inadequate, and we therefore doubled it.”) But despite 60 years since dexamethasone’s introduction, we still don’t have much more insight into the right regimen for ED presentations of asthma (it was Slater who settled on 12mg of dexamethasone, to keep a 1:5 ratio with 60 mg of prednisone).
I’d love to see more research into the right ED therapy for asthma. The Cochrane review points out many worthwhile avenues for future research into drug, dose, and regimen. In the meantime, however, when I think an asthma patient may be unable to fill their prednisone prescription, I’ll reach for a one-time dose of 12mg of dexamethasone.
REFERENCES
- 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(10):1111-5.
- M.W. Rehrer, B. Liu, M. Rodriguez, et al. A randomized controlled noninferiority trial of single dose of oral dexamethasone versus 5 days of oral prednisone in acute adult asthma. Ann Emerg Med 2016; 68(5): 608-613.
- Carson MP. Editorial oversight of results reported in Annals. Ann Emerg Med 2016; 68(6): 787-788.
- Aboeed A, Mathew JJ, Manickavel S, Riss A, McNamee J, Debari V, et al. Dexamethasone versus prednisone in the treatment of acute asthma in adults: can an easier regimen provide the same results?. American Journal of Respiratory and Critical Care Medicine 2014;189:A1360.
- Normansell R, Kew KM, Mansour G. Different oral corticosteroid regimens for acute asthma. Cochrane Database of Systematic Reviews 2016, Issue 5. Art. No.: CD011801.
- Slater JD, et al. Clinical and metabolic effects of dexamethasone. Lancet 1959; 1(7065):173-7.
