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Communications to the Editor |

Low- vs High-Dose Inhaled Albuterol for the Treatment of Acute Asthma Low- vs High-Dose Inhaled Albuterol for the Treatment of Acute Asthma FREE TO VIEW

Michael J. Asmus, PharmD; Leslie Hendeles, PharmD
Author and Funding Information

Affiliations: University of Florida, Gainesville, FL ,  MetroHealth Medical Center, Cleveland, OH

Correspondence to: Michael J. Asmus, PharmD, University of Florida Health Science Center, PO Box 100486, Gainesville, FL 32610-0486; e-mail: asmus@cop.uFl.edu



Chest. 1999;116(2):585-586. doi:10.1378/chest.116.2.585-a
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To the Editor:

We read with interest the clinical trial recently published by Emerman et al (January 1999)1comparing the administration of nebulized albuterol, 2.5 mg, to the administration of nebulized albuterol, 7.5 mg, in the treatment of acute asthma in the emergency department setting. The study was obviously conducted with scientific rigor, and the results cannot be disputed. However, we would like to offer an alternative explanation for the absence of a significant difference between these treatments. The choice of albuterol solution may have played a role in this study. The presence of benzalkonium chloride (BAC), a preservative that produces bronchoconstriction in a dose-dependent manner,2may have antagonized the bronchodilator effects of albuterol.3 For example, a 2.5-mg dose of albuterol contains 50 μg BAC in the unsterile multidose dropper bottle and 300 μg BAC in the unsterile unit-dose screw-cap vial, whereas the sterile-filled unit-dose vial contains no BAC. According to Dr. Emerman, the unsterile multidose dropper bottle (50 μg BAC/2.5 mg albuterol) was used in this study (personal communication; January 1999). Therefore, patients randomized to high-dose albuterol received 150 μg BAC every 20 min for a total of 450 μg. This is well within the range of BAC doses known to decrease forced expiratory volume by ≥ 20% in asymptomatic volunteers with asthma.2 It is unlikely that patients randomized to the low-dose regimen would be affected by the presence of BAC since they would have received a total dose of 150 μg, which is below the threshold dose. Thus, it is possible that the high-dose albuterol treatment did not provide greater bronchodilation because the effects were diminished by BAC-induced bronchoconstriction.

Emerman, CL, Cydulka, RK, McFadden, ER (1999) Comparison of 2.5 vs 7.5 mg of inhaled albuterol in the treatment of acute asthmaChest115,92-96. [CrossRef]
 
Zhang, YG, Wright, WJ, Tam, WK, et al Effects of inhaled preservatives on asthmatic subjects: II. Benzalkonium chloride.Am Rev Respir Dis1990;141,1405-1408. [CrossRef]
 
Beasley, R, Fishwick, D, Miles, JF, et al Preservatives in nebulizer solutions: risks without benefit.Pharmacotherapy1998;18,130-139
 

Low- vs High-Dose Inhaled Albuterol for the Treatment of Acute Asthma

To the Editor:

The work of Beasley and Hendeles,1 raises some interesting points about the presence of benzalkonium chloride (BAC) as a preservative in albuterol solution. As noted by the authors, previous work has indicated that benzalkonium chloride does act as a bronchoconstrictor when administered to patients who are also given inhaled histamine. The question for the clinician is whether or not the addition of BAC to albuterol solution in current clinical doses leads to paradoxical bronchial constriction. It is not at all clear from previous reports that this is the case. The response to histamine challenge is certainly different from judging the efficacy of a potent bronchodilator mixed with BAC. Furthermore, albuterol-free solution is not readily available in forms other than sterile unit dose vials. Unfortunately, the clinician would have to administer 9 mL of inhalation fluid in order to use standard albuterol-free unit dose vials to reproduce our study.

The effect of these considerations for the clinician is probably the same. Whether or not BAC limits the effectiveness of high- dose albuterol, or high-dose albuterol administered in repeated doses is more effective than repeated doses of 2.5 mg of albuterol, we confirm the conclusion of our article (January 1999).2 It would be interesting to repeat our study using BAC-free albuterol solution in a concentration that is consistent with the usual volumes of fluid used in nebulization. For the moment however, we again must conclude that there is not sufficient evidence to warrant giving repeated doses of high-dose albuterol in most asthmatic patients.

References
Beasley, R, Hendeles, L Preservatives in nebulizer solutions: risks without benefits; a further comment.Pharmacotherapy1999;19,473-474. [CrossRef]
 
Emerman, CL, Cydulka, RK, McFadden, ER Comparison of 2.5 vs 7.5 mg of inhaled albuterol in the treatment of acute asthmaChest1999;115,92-96. [CrossRef]
 

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References

Emerman, CL, Cydulka, RK, McFadden, ER (1999) Comparison of 2.5 vs 7.5 mg of inhaled albuterol in the treatment of acute asthmaChest115,92-96. [CrossRef]
 
Zhang, YG, Wright, WJ, Tam, WK, et al Effects of inhaled preservatives on asthmatic subjects: II. Benzalkonium chloride.Am Rev Respir Dis1990;141,1405-1408. [CrossRef]
 
Beasley, R, Fishwick, D, Miles, JF, et al Preservatives in nebulizer solutions: risks without benefit.Pharmacotherapy1998;18,130-139
 
Beasley, R, Hendeles, L Preservatives in nebulizer solutions: risks without benefits; a further comment.Pharmacotherapy1999;19,473-474. [CrossRef]
 
Emerman, CL, Cydulka, RK, McFadden, ER Comparison of 2.5 vs 7.5 mg of inhaled albuterol in the treatment of acute asthmaChest1999;115,92-96. [CrossRef]
 
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