Albuterol enantiomer levels, lung function and QTc interval in patients with acute severe asthma and COPD in the emergency department

Abstract

Background: This observational study was designed to investigate plasma levels of albuterol enantiomers among patients with acute severe asthma or COPD presenting to the emergency department, and the relationship with extra-pulmonary cardiac effects (QTc interval) and lung function. Recent reviews have raised concerns about the safety of using large doses of β2-agonists, especially in patients with underlying cardiovascular comorbidity. It has been demonstrated that significant extrapulmonary effects can be observed in subjects given nebulised (R/S)-albuterol at a dose of as little as 6.5 mg.

Methods: Blood samples were collected and plasma/serum levels of (R)- and (S)-albuterol enantiomers were determined by LC-MS and LC-MS/MS assay. Extra-pulmonary effects measured at presentation included ECG measurements, serum potassium level and blood sugar level, which were collected from the hospital medical records.

Results: High plasma levels of both enantiomers were observed in some individuals, with median (range) concentrations of 8.2 (0.6-24.8) and 20.6 (0.5-57.3) ng/mL for (R)- and (S)- albuterol respectively among acute asthma subjects, and 2.1 (0.0-16.7) to 4.1 (0.0-36.1) ng/mL for (R)- and (S)- albuterol respectively among COPD subjects. Levels were not associated with an improvement in lung function or adverse cardiac effects (prolonged QTc interval).

Conclusions: High plasma concentrations of albuterol were observed in both asthma and COPD patients presenting to the emergency department. Extra-pulmonary cardiac adverse effects (prolonged QTC interval) were not associated with the plasma level of (R)- or (S)-albuterol when administered by inhaler in the emergency department setting. Long-term effect(s) of continuous high circulating albuterol enantiomer concentrations remain unknown, and further investigations are required.

Figure 1

Plasma albuterol enantiomer levels observed among subjects presenting with acute asthma exacerbation (n = 15).

Figure 2

Serum albuterol enantiomer levels observed among subjects presenting with acute exacerbation of COPD (n = 30).

Figure 3

Relationship between QTc interval and albuterol levels. Recorded QTc interval and (R)-, (S)- and total albuterol levels and are shown in (a), (b) and (c) respectively. (R)-, (S)- and total albuterol levels in subjects with normal or prolonged QTc interval are shown in (d), (e) and (f).