Inhaled beta2-agonists are a key component of the initial treatment of acute asthma. Guidelines recommend repeated doses of albuterol for emergency treatment of acute asthma, but many patients show little or no response to this regimen. This finding may in part be explained by the fact that albuterol is a weak partial agonist (low intrinsic efficacy). Our study examines the efficacy and safety of isoproterenol (full agonist) versus albuterol in adults presenting with acute severe asthma.
In a double-blind study, adults (18-50 years) presenting with acute severe asthma (FEV1 < 50%) were randomized to albuterol (7.5 mg/hour) (n = 10, mean % predicted FEV1 = 37%) or isoproterenol (7.5 mg/hour) (n = 9, mean % predicted FEV1 = 33.3%) administered for two hours by continuous nebulization. Efficacy measures and safety parameters were collected.
Both groups had similar baseline characteristics. The improvements in baseline FEV1 at 60 and 120 minutes were significantly higher in subjects receiving isoproterenol compared to those receiving albuterol (44.2 vs. 17.4% and 62.6 vs. 23.5%, respectively, p < 0.05). The change in Modified Borg scores was also significantly greater in subjects receiving isoproterenol at 45, 60, 90, 105 and 120 minutes (p < 0.01). Both treatments were well tolerated. However, the change in pulse rate from baseline was significantly higher in the isoproterenol group compared to the albuterol group (22.4% vs. 6.9%, respectively, p<0.05). The decrease in serum potassium from baseline was also significantly greater in the isoproterenol group compared to the albuterol group (-0.52 vs. -0.07 meq/L, respectively, p <0.05).
Our data suggest that the intrinsic efficacy of a beta2-agonist is an important determinant of the physiologic and symptomatic response in acute severe asthma.
Patients with acute severe asthma who have an inadequate response to an agonist of low intrinsic efficacy may benefit from use of an agonist of a higher intrinsic efficacy.
N.A. Hanania, None.