If there were a better, cheaper, shorter alternative to a five-day course of prednisone for patients with acute asthma exacerbation, would emergency physicians prescribe it? An interesting study recently weighed in on whether to use oral dexamethasone instead of prednisone to treat acute asthma.
Acute asthma is a common presentation in adult and pediatric emergency departments, accounting for almost two million ED visits in the United States per year. (NCHS Vital Health Stat 2011;13.) Corticosteroids have long been used in emergency departments to treat acute asthma exacerbations, and have been shown to be effective in avoiding admission (Cochrane Database Syst Rev 2001;:CD002178) and avoiding ED relapse (Cochrane Database Syst Rev 2001;:CD000195) when used in conjunction with bronchodilator therapy.
Recommended corticosteroids include oral and parenteral preparations of systemic steroids, which have been found equally effective. (Chest 2001;126:362.) Of course, the oral route is usually preferred, being less painful and invasive. Oral prednisone and dexamethasone are the currently recommended systemic steroids for moderate to severe asthma exacerbations. Theoretically, dexamethasone has the advantage of a much longer half-life than prednisone, but few trials have compared oral dexamethasone head-to-head with oral prednisone. In fact,-before the adult study by Kravitz et al, two pediatric trials dominated the scene.
One study compared two days of dexamethasone (0.6 mg/kg daily; maximum 16 mg/day) to five days of prednisone (1 mg/kg daily; maximum 60 mg/day) in 2- to 18-year-olds with acute asthma in the ED. (J Pediatr 2001;139:20.) Dexamethasone was shown to be equivalent to prednisone in relapse rates, admissions, and persistence of symptoms at 10 days, but had the added benefits of increased compliance and fewer side effects, such as vomiting. Better compliance, however, may have been partly due to the study design because patients were discharged from the ED with the second dose of dexamethasone, while patients in the prednisone arm had to fill a prescription for their five-day course. Unfortunately, this study was also limited by its unblinded design and a mid-study change in protocol.
Another pediatric trial in 2006 compared a single dose of dexamethasone (0.6mg/kg) with five days of prednisolone (2 mg/kg daily) in children 2-16 with mild to moderate asthma. (Pediatr Emerg Care 2006;22:786.) This study demonstrated no difference in hospital admission rates,-additional beta–agonist therapy, or return to patient self-assessment baseline scores, although the trial was-underpowered.
Taken together, these studies suggest that no significant difference exists between prednisone and dexamethasone in the ability to treat acute asthma exacerbations effectively in the pediatric population, and perhaps there are some benefits to dexamethasone for vomiting and compliance profiles.
The Kravitz trial was randomized, double-blinded, and controlled. Patients 18 to 45 with asthma exacerbation were treated with standard doses of albuterol and ipratropium bromide at the discretion of the treating physician. A total of 257 patients were then randomized to receive either prednisone (60 mg/d x 5 days) or dexamethasone (16 mg/day x 2 days, then 3 days of placebo). In each group, the first dose of steroid was administered in the ED. Subsequent doses were distributed to patients upon discharge with instructions to take tablets at home in numbered sequence over the following four days.
The study's primary outcome was return to normal activity within three days. More patients in the dexamethasone group (90%) than the prednisone group (80%) returned to normal activity within this interval (10% difference; 95% CI 0% to 20%; p=0.49). The frequency of asthma relapse was similar in each group.
A few limitations of the study are worth mentioning. First, a validated instrument was not used to measure improvement in asthma symptoms or lung function, though one could argue that a return to baseline activity is perhaps an even better clinical endpoint. Although return to normal function at three days was the main endpoint, this was not measured or determined until a full two weeks after the ED visit. Rather than depend on a patient's ability to recall prior events, it would have been preferable (and probably much more accurate) to perform the follow-up interview on the same day patient symptoms were to be assessed. Finally, a significant 22 percent of patients (57/257) were lost to follow-up.
Despite these limitations, this study brings dexamethasone to the forefront as a viable alternative to prednisone for treating mild to moderate asthma exacerbations in adults. Hopefully future studies will determine if the same clinical response can be achieved with a lower dose (or perhaps even a single dose) of dexamethasone.
For now, continue administering first-dose glucocorticoid for adults with mild to moderate asthma exacerbations while they are still in the ED. The evidence is overwhelming that this will benefit your patients. One should consider, however, using dexamethasone instead of prednisone. Worst-case scenario, it seems dexamethasone 16 mg for two days is equivalent to prednisone 60 mg for five days. But the best-case scenario is that dexamethasone actually results in a 10 percent higher rate of functional recovery after three days. When one considers the likely benefit of better compliance with a two-day regimen, the scale tips even more favorably toward dexamethasone.
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