HEMODYNAMIC, CARDIAC, AND ELECTROLYTE EFFECTS OF LOW-DOSE AEROSOLIZEDTERBUTALINE SULFATE IN ASTHMATIC-PATIENTS

Study objective: Aerosolized beta(2)-agonists have been associated wit h increased morbidity in asthmatics, These drugs cause transient incre ases in heart rate and decreases in serum potassium levels after these drugs are first utilized. This study is designed to elucidate whether beta-adrenergic tolerance to the hemodynamic, cardiac, and electrolyt e effects of inhaled terbutaline occurs during 14 days of maintenance therapy. Design: Eight patients with stable asthma weaned off beta(2)- agonist therapy were studied in a randomized, double-blinded, placebo- controlled study utilizing aerosolized terbutaline, 400 mu g q6h. Hemo dynamic measurements and M-mode echocardiography were performed before and 15 and 30 min after the initial dose of terbutaline or placebo an d after a dose of aerosolized terbutaline after 14 days of aerosolized terbutaline maintenance therapy. Holter monitors were worn on the fir st day of placebo or terbutaline therapy and on day 14 of terbutaline therapy. Plasma potassium, bicarbonate, sand glucose levels, pH, renin activity, and serum insulin and aldosterone levels were measured befo re and after 24 and 48 h after terbutaline or placebo therapy and afte r 14 days of aerosolized terbutaline maintenance therapy, Results: Ter butaline increased cardiac index and decreased systemic vascular resis tance greater after 14 days of therapy compared with the first dose (5 .2+/-0.5 vs 4.4+/-0.6 L/min/m(2); p<0.05; and 760+/-62 vs 1,016+/-118 dyne . s . cm(-5), p<0.01). After 14 days of terbutaline therapy, the mean maximum heart rate and number of episodes of heart rate >100 beat s/min were higher compared with the other study day (p <0.05). Plasma potassium level decreased from 4.29+/-0.09 to 3.65+/-0.16 mmol/L after 24 h of terbutaline and to 3.90+/-0.11 mmol/L after 48 h. Plasma pota ssium level returned to baseline after 14 d of terbutaline therapy. Pl asma glucose and serum insulin levels rose significantly 24 h and 48 h after terbutaline and returned to baseline after 14 d of terbutaline therapy. Serum aldosterone level decreased significantly as serum pota ssium level decreased in the fit-st 48 h of terbutaline therapy but re turned to baseline levels after 14 d of terbutaline, Conclusions: Card oivascular beta(2)-receptors in patients with stable asthma do not dev elop tolerance to the effects of low-dose aerosolized terbutaline afte r 14 days of maintenance therapy. In contrast, the homeostatic mechani sms regulating serum potassium develop tolerance to low-dose terbutali ne maintenance therapy, Lack of cardiovascular tolerance to maintenanc e doses of aerosolized beta(2)-agonists may be important in increased morbidity if excessive amounts of these drugs are administered during asthma exacerbations.