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

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.