Levalbuterol for Severe Acute Asthma in Children?
Andrews T, McGintee E, Mittal MK, et al
J Pediatr. 2009;155:205-210
Racemic albuterol (RAC) is a mixture of (R) and (S) isomers of albuterol; levalbuterol (LEV) contains just the (R) isomer. The adult and pediatric data are mixed on whether LEV performs better than RAC in emergent settings, but the largest emergency department (ED) trial in children suggested that LEV reduced hospitalization rates. In that trial and others, LEV and comparators were administered in intermittent dosing.
This randomized controlled trial differed by randomizing after children failed ED management with intermittent bronchodilators. The subjects received continuous therapy for at least the first hour after admission. The subjects were enrolled in the pediatric ED at a large, urban children's hospital. Patients were 6-19 years old, and all had at least 2 previous episodes of lifetime wheezing.
In the ED, patients were treated with a standard approach that included three 5-mg doses of albuterol (RAC), 2 ipratropium bromide inhalations, and oral prednisolone in the first hour after presentation. If subjects did not experience sufficient improvement after the first hour, they were eligible for enrollment, excluding patients admitted to the intensive care unit and those with chronic medical conditions (other than asthma) that might affect results.
Subjects were randomized to receive either 20 mg of RAC or 10 mg of LEV per hour. Patients were assessed hourly, and a condition of "severe," "moderate," or "mild" was assigned. If subjects experienced 2 subsequent condition assignments of moderate or mild, the dose of continuous medication was reduced by half. With 2 additional condition assessments of moderate or mild, the subjects were changed to intermittent dosing of RAC.
The primary outcome of interest was duration of continuous therapy, with asthma score being a secondary outcome. Over a 2-year period, the investigators sought to enroll 143 eligible subjects; about half of the subjects approached agreed to participate. Forty patients were randomized to RAC and 41 to LEV. The groups were similar for most baseline characteristics -- with the sample being approximately 63% boys, 93% black, and similar asthma severity scores.
In the primary analysis, there was no difference in the duration of continuous therapy between the 2 groups whether the difference was measured by mean (20.1 hours for RAC and 19.8 hours for LEV group) or median (18.3 hours for RAC and 16.0 hours for LEV group) duration of continuous therapy. In addition, the median time until fit for discharge was 45 hours for RAC and 46 hours for LEV. There were no differences in the asthma severity scores or individual clinical measures, such as respiratory rates, pulse oximetry readings, etc, across the time of therapy.
The authors concluded that there is no benefit to using LEV instead of RAC for continuous treatment of status asthmaticus after failing initial ED treatment.
It is important to recognize the limitations of the application of these data. First, it is important to note that both the authors and accompanying editorialists noted that the largest randomized trial in children using intermittent RAC compared with LEV demonstrated a lower hospitalization rate in children receiving LEV. That trial had its own limitations, but it did include a large sample of more than 500 children. The study reviewed here took place after the initial failure of ED treatment, so it does not obviate the possibility that LEV may provide benefit by intermittent use upon presentation to the ED. Instead, it means that the investigators were unable to demonstrate a benefit after admission. I was most struck by the overall lack of difference in time to discharge. Although children in the RAC group in this study were more likely to relapse into need for continuous therapy once weaned to intermittent, this made no difference in overall hospital time, the largest driver of asthma costs from the hospital standpoint. Given the fact that LEV is more expensive than RAC, its use after admission may not be warranted.
Abstract
High-Dose Continuous Nebulized Levalbuterol for Pediatric Status Asthmaticus: A Randomized Trial
Andrews T, McGintee E, Mittal MK, et al
J Pediatr. 2009;155:205-210
Summary
Racemic albuterol (RAC) is a mixture of (R) and (S) isomers of albuterol; levalbuterol (LEV) contains just the (R) isomer. The adult and pediatric data are mixed on whether LEV performs better than RAC in emergent settings, but the largest emergency department (ED) trial in children suggested that LEV reduced hospitalization rates. In that trial and others, LEV and comparators were administered in intermittent dosing.
This randomized controlled trial differed by randomizing after children failed ED management with intermittent bronchodilators. The subjects received continuous therapy for at least the first hour after admission. The subjects were enrolled in the pediatric ED at a large, urban children's hospital. Patients were 6-19 years old, and all had at least 2 previous episodes of lifetime wheezing.
In the ED, patients were treated with a standard approach that included three 5-mg doses of albuterol (RAC), 2 ipratropium bromide inhalations, and oral prednisolone in the first hour after presentation. If subjects did not experience sufficient improvement after the first hour, they were eligible for enrollment, excluding patients admitted to the intensive care unit and those with chronic medical conditions (other than asthma) that might affect results.
Subjects were randomized to receive either 20 mg of RAC or 10 mg of LEV per hour. Patients were assessed hourly, and a condition of "severe," "moderate," or "mild" was assigned. If subjects experienced 2 subsequent condition assignments of moderate or mild, the dose of continuous medication was reduced by half. With 2 additional condition assessments of moderate or mild, the subjects were changed to intermittent dosing of RAC.
The primary outcome of interest was duration of continuous therapy, with asthma score being a secondary outcome. Over a 2-year period, the investigators sought to enroll 143 eligible subjects; about half of the subjects approached agreed to participate. Forty patients were randomized to RAC and 41 to LEV. The groups were similar for most baseline characteristics -- with the sample being approximately 63% boys, 93% black, and similar asthma severity scores.
In the primary analysis, there was no difference in the duration of continuous therapy between the 2 groups whether the difference was measured by mean (20.1 hours for RAC and 19.8 hours for LEV group) or median (18.3 hours for RAC and 16.0 hours for LEV group) duration of continuous therapy. In addition, the median time until fit for discharge was 45 hours for RAC and 46 hours for LEV. There were no differences in the asthma severity scores or individual clinical measures, such as respiratory rates, pulse oximetry readings, etc, across the time of therapy.
The authors concluded that there is no benefit to using LEV instead of RAC for continuous treatment of status asthmaticus after failing initial ED treatment.
Viewpoint
It is important to recognize the limitations of the application of these data. First, it is important to note that both the authors and accompanying editorialists noted that the largest randomized trial in children using intermittent RAC compared with LEV demonstrated a lower hospitalization rate in children receiving LEV. That trial had its own limitations, but it did include a large sample of more than 500 children. The study reviewed here took place after the initial failure of ED treatment, so it does not obviate the possibility that LEV may provide benefit by intermittent use upon presentation to the ED. Instead, it means that the investigators were unable to demonstrate a benefit after admission. I was most struck by the overall lack of difference in time to discharge. Although children in the RAC group in this study were more likely to relapse into need for continuous therapy once weaned to intermittent, this made no difference in overall hospital time, the largest driver of asthma costs from the hospital standpoint. Given the fact that LEV is more expensive than RAC, its use after admission may not be warranted.
Abstract
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