Chest
Volume 129, Issue 1, January 2006, Pages 124-132
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Original Research: Airway Secretions
Assessing the Effects of Racemic and Single-Enantiomer Albuterol on Airway Secretions in Long-term Intubated Patients

https://doi.org/10.1378/chest.129.1.124Get rights and content

Objective: In vitro

data suggest that the S-enantiomer of albuterol can induce mucociliary dysfunction. This clinical study assesses the clinical significance of standard doses of the S-enantiomer on airway secretions in long-term intubated patients by comparing a racemic formulation of albuterol, an R-enantiomer formulation, and normal saline solution.

Design

A placebo-controlled crossover study.

Patients

Fourteen stable intubated patients with a median duration of intubation of 21 months and a median age of 72 years.

Setting

Long-term ventilator unit in skilled nursing facility.

Interventions

Following a 2-week washout period during which regularly scheduled β2-agonists were discontinued, tracheal aspirates were collected for 4 h/d for a 5-day period to establish baseline values, and the patients were then randomized in crossover manner to each of three nebulized treatments: normal saline solution, racemic albuterol, and R-albuterol. Each treatment was administered three times daily for 5 days, followed by a 2-day washout.

Measurements

Tracheal aspirates were analyzed for volume, sodium, chloride, bicarbonate, interleukin (IL)-8, IL-1β, soluble intercellular adhesion molecule, and tumor necrosis factor-α.

Results

There were no consistent significant differences among the three treatment periods either in terms of volume of secretions or in the concentrations of the electrolytes or the inflammatory indexes. However, all three treatments, including saline solution, were associated with increased secretion volume after the first dose, but this effect was not apparent on subsequent doses.

Conclusion

There were no significant differences between racemic albuterol and R-albuterol observed in this study for any of the parameters studied, suggesting that the S-enantiomer does not adversely affect airway secretions at recommended doses. In addition, the routine administration of nebulized β2-sympathomimetic agonists to stable patients undergoing prolonged intubation, for the sole purpose of changing the volume and composition of secretions of airway secretions, is not supported by the results of this study.

Section snippets

Study Design

This is a placebo-controlled crossover study. During a 2-week washout period, regularly scheduled β2-agonists were discontinued. Patients then underwent daily measurements of secretion volume for 1 week with no aerosolized medications. The patients then received a series of three nebulized treatments in random order during consecutive weeks: normal saline solution, generic racemic albuterol, and R-albuterol. The racemic albuterol and R-albuterol were supplied by the manufacturers as premixed

Results

In Figure 2, the data from individual subjects are illustrated with each set of four bar graphs representing the sum of 5 days of aspirate volumes for the control period and each of the three treatment periods. Each data point in Figure 2, top, a, and bottom, b, represents the sum of five individual timed daily volume measurements. Figure 2, top, a, presents data for the 5-day aggregate of first-hour volumes, while Figure 2, bottom, b, presents the 5-day aggregate volumes at 4 h. Table 2 shows

Discussion

This is the first clinical study to compare the effects of a racemic and a single-enantiomer formulation on airway secretion in any population, and the first study to objectively evaluate the impact of β2-sympathomimetic agonists on secretory function in tracheostomized patients receiving mechanical ventilation, and only the second study of the effects of these agents on secretion volume. We report that all treatments, including saline solution, were associated with a transient increase in

Acknowledgment

We thank the Respiratory Care Department staff and the nursing staff of Floor Four East, Gurwin Jewish Geriatric Center, Commack, NY, for their cooperation with the study. We thank Teresa Kramer, RN, ANP, April Plank, RN, ANP, and Barbara Starke, RN, ANP, for the specimen collection. We thank Mohammed Amin, MD, and Akbar Shah, MD, for performing the ventilator bench testing, and Mr. Robert Perry for performing the cytokine assays.

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    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

    This study was supported by a grant from Sepracor Inc., Marlborough, MA.

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