Comparison of racemic albuterol and levalbuterol in the treatment of acute asthma in the ED

Abstract

Background

Acute asthma is often treated with racemic albuterol, a 1:1 mixture of (R)-albuterol and (S)-albuterol. Levalbuterol is the single-isomer agent comprised (R)-albuterol, an active bronchodilator, without any effects of (S)-albuterol.

Objective

To compare emergency department (ED) admission rates of patients presenting with acute asthma who were treated with either racemic albuterol or levalbuterol.

Setting

Suburban community teaching hospital.

Design

Retrospective observational case review.

Methods

Emergency department patients presenting with acute asthma at 2 different sites were reviewed over 9- and 3-month consecutive periods. Outcome measures included ED hospital admission rate, length of stay, arrival acuity, and treatment costs. Patients were excluded if younger than 1 year or if no treatment of acute asthma was rendered.

Results

Of the initial 736 consecutive cases, significantly fewer admissions (4.7% vs 15.1%, respectively; P = .0016) were observed in the levalbuterol vs racemic albuterol group. Of the subsequent 186 consecutive cases, significantly fewer admissions were also observed (13.8% vs 28.9%, respectively; P = .021) in the levalbuterol vs racemic albuterol group. Treatment costs were lower with levalbuterol mainly because of a decrease in hospital admissions.

Conclusion

Levalbuterol treatment in the ED for patients with acute asthma resulted in higher patient discharge rates and may be a cost-effective alternative to racemic albuterol.

Introduction

Asthma is one of the most common illnesses treated in the emergency department (ED) setting. It is reported that nearly 15 million Americans have asthma, and the more than 2 million annual ED visits result in costs in excess of $6 billion with hospitalizations accounting for the largest portion of these costs [1], [2], [3], [4]. In the United States from 1992 to 1999, the absolute number and rate of ED visits for asthma increased by 36% and 29%, respectively [4]. An evaluation of 1 448 555 consecutive patients presenting to 15 EDs in northern New Jersey from 1997 to 1999 demonstrated an increasing number of asthma visits (Fig. 1). In addition, an increasing proportion of asthma-related hospital admissions from the ED was also reported. In the calendar year 1999, it was shown that 2.7% of all ED admissions were due to acute asthma and the average acute asthma admission rate from 1997 to 1999 was 16.4% across the 15 northern New Jersey EDs studied (Emergency Medical Associates, Livingston, NJ).

Multiple therapeutic modalities are available to the ED physician to manage acute asthmatic episodes, including β₂-adrenergic agonists and corticosteroids, which are the mainstays of therapy. The most widely prescribed therapy for asthma in the inpatient, outpatient, and ED settings are the β₂-adrenergic agonists. Human β₂-adrenergic receptors are specifically designed to allow a conformational fit with l-epinephrine, the (R)-stereoisomer. Synthetic β₂-adrenergic agonists such as racemic albuterol structurally mimic epinephrine and bind to the β₂-adrenergic receptor site [5]. Racemic albuterol, the most commonly used β₂-adrenergic agonist, is a 1:1 mixture of (R)- and (S)-albuterol stereoisomers. (R)-albuterol, also known as levalbuterol, solely binds to the β₂-adrenergic receptor, producing bronchodilation, whereas (S)-albuterol, because of its structural conformation, does not effectively bind to the β₂-adrenergic site and has been considered inert for more than 30 years [6]. Only after the clinical acceptance and use of racemic albuterol was the technology to separate stereoisomers (enantiomers) developed, enabling the investigation of the individual properties of (R)- and (S)-albuterol. Since then, experiments with animal, tissue, and cell culture models have suggested that (S)-albuterol has proinflammatory effects [7], [8] and that it enhances airway tissue hyperresponsiveness and contractile responses [9], [10], [11]. Furthermore, (S)-albuterol has a 10-fold slower rate of metabolism than (R)-albuterol and, with frequent dosing, can accumulate in patients' plasma and lung tissue in the absence of (R)-albuterol [12], [13], [14]. A more recent report has corroborated the proinflammatory dose- and time-dependent effects of (S)-albuterol and has discussed some of the mechanisms and pathways involved [15].

The development of new technology allowing the separation of the (R)- and (S)-albuterol stereoisomers has resulted in the development of a pure levalbuterol formulation (Xopenex, Sepracor, Marlborough, Mass). This formulation has been approved for the treatment of bronchoconstriction in patients 6 years and older, but justification of its higher acquisition cost relative to its therapeutic efficacy is controversial. The purpose of this study was to compare the overall disposition and economic impact on patients with acute asthma treated in the ED setting who received either levalbuterol or racemic albuterol as part of their primary therapy.