Continuous versus Intermittent Nebulized Terbutaline: Plasma Levels and Effects

Abstract

The purpose of this investigation was to compare continuous versus intermittent nebulization of a β-agonist, terbutaline, to determine whether differences exist in plasma concentrations or adverse cardiovascular effects of the drug with these two techniques for its administration. Sixteen children 6 to 16 yr of age, admitted for acute asthma, were enrolled in this randomized double-blind clinical trial. Nebulization of 16 mg of terbutaline over an 8-h period was performed either continuously or intermittently, with a dose of 4 mg given over 20 min every 2 h. The peak plasma terbutaline concentration for the intermittent nebulization treatment (INT) group (5.1 ± 2.1 ng/ml) occurred 1 h after the fourth inhalation treatment and was similar to the peak concentration for the continuous nebulization treatment (CNT) group, which was reached at the end of the 8 h period (4.7 ± 2.3 ng/ml). The maximum heart rate increase for the INT group (19.6 ± 18.3 bpm) occurred 1 h after the fourth dose and was similar to the peak observed in the CNT group (19.6 ± 19.2 bpm), which occurred after 3 h. Similar increases in systolic and decreases in diastolic pressures were observed for the INT and CNT groups. No evidence of serious adverse myocardial complications was seen in either group, as evidenced by measurements of the MB fraction of creatine phosphokinase (CPK-MB) and Holter-monitor recordings. Continuous nebulization of the terbutaline produces similar plasma concentrations and cardiovascular physiologic responses as intermittent nebulization. These findings suggest that the improved therapeutic efficacy of frequent or continuous β-agonist administration is not secondary to a greater systemic drug concentration achieved with this technique but rather to more optimal direct local pulmonary effects.