CONTINUOUS VERSUS INTERMITTENT NEBULIZED TERBUTALINE - PLASMA-LEVELS AND EFFECTS

The purpose of this investigation was to compare continuous versus int ermittent nebulization of a beta(2)-agonist, terbutaline, to determine whether differences exist in plasma concentrations or adverse cardiov ascular effects of the drug with these two techniques for its administ ration. Sixteen children 6 to 16 yr of age, admitted for acute asthma, were enrolled in this randomized double-blind clinical trial. Nebuliz ation 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 intermitt ent nebulization treatment (INT) group (5.1 +/- 2.1 ng/ml) occurred 1 h after the fourth inhalation treatment and was similar to the peak co ncentration for the continuous nebulization treatment (CNT) group, whi ch was reached at the end of the 8 h period (4.7 +/- 2.3 ng/ml). The m aximum heart rate increase for the INT group (19.6 +/- 18.3 bpm) occur red 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 i ncreases in systolic and decreases in diastolic pressures were observe d for the INT and CNT groups. No evidence of serious adverse myocardia l complications was seen in either group, as evidenced by measurements of the MB fraction of creatine phosphokinase (CPK-MB) and Holter-moni tor recordings. Continuous nebulization of the terbutaline produces si milar plasma concentrations and cardiovascular physiologic responses a s intermittent nebulization. These findings suggest that the improved therapeutic efficacy of frequent or continuous beta(2)-agonist adminis tration is not secondary to a greater systemic drug concentration achi eved with this technique but rather to more optimal direct local pulmo nary effects.