Acute effects of higher than customary doses of salmeterol and salbutamol in patients with acute exacerbation of COPD

AbstractWorsening of underlying bronchospasm may be associated with acute exacerbations of chronic obstructive pulmonary disease (COPD). As airway obstruction becomes more severe, the therapeutic option is to add salbutamol, but not salmeterol, as needed to cause rapid relief of bronchospasm. Unfortunately, the most effective dosage ofβ2 -agonists may increase above that recommended during acute exacerbations. In this study, we compared the acute effects of higher than customary doses of salmeterol and salbutamol in 20 patients with acute exacerbation of COPD. A dose–response curve to salmeterol pMDI, 25 μg/puff, or salbutamol pMDI, 100 μg/puff, was constructed using 1, 1, and 2 puff's i.e., a total cumulative dose of 100 μg salmeterol or 400 μg salbutamol on 2 consecutive days. After baseline measurements, dose increments were given at 30-min intervals with measurements being made 25 min after each dose. Heart rate (HR) and pulse-oximetry (S pO2) measurements were then taken. Both salmeterol and salbutamol induced a large and significant (P<0.05) dose-dependent increase in FEV1 [mean differences from baseline (L) = after 100 μg salmeterol: 0.174 (95% CI: 0.112 to 0.237); after 400 μg salbutamol: 0.165 (95% CI: 0.080 to 0.249)], in IC [mean differences from baseline (L) = after 100 μg salmeterol: 0.332 (95% CI: 0.165 to 0.499); after 400 μg salbutamol: 0.281 (95% CI: 0.107 to 0.456)] (Fig. 2), and in FVC mean differences from baseline (L) = after 100 μg salmeterol: 0.224 (95% CI: 0.117 to 0.331); after 400 μg salbutamol: 0.242 (95% CI: 0.090− to 0.395)]. There was no significant difference between the FEV1 values (P=0.418), the IC values (P=0.585), and the FVC value (P= 0.610) after 100 μg salmeterol and 400 μg salbutamol. HR [mean differences from baseline (beats/min) = after 100 μg salmeterol: 3.15 (95% CI: −0.65 to 6.96); after 400 μg salbutamol: 2.30 (95% CI: −0.91 to 5.51)] and S pO2 [mean differences from baseline (%) = after 100 μg salmeterol: −0.20 (95% CI: −1.00 to 0.60); after 400 μg salbutamol: −0.11 (95% CI: −1.00 to 0.79)] did not change significantly from baseline (P>0.05). These data indicate that salmeterol is effective and safe in the treatment of acute exacerbation of COPD and support its use in this clinical condition