Effect of β₂-adrenoceptor agonists on plasma potassium and cardiopulmonary responses on exercise in patients with chronic obstructive pulmonary disease

Objective: The effect of β₂-adrenoceptor agonist-induced hypokalaemia on cardiac arrhythmias might be exacerbated during exercise, especially in patients with more compromised airway function. Methods: To evaluate the effect of β₂-adrenoceptor agonists on plasma potassium and cardiopulmonary function during exercise, two identical submaximal treadmill exercise tests were performed, at least 48 h apart, by 13 patients with moderate to severe COPD (11 men and 2 women, mean age 66 y, mean FEV₁/FVC ratio 48.9 (2.8)%) 30 min after they had received nebulised fenoterol or salbutamol (2 mg). The experiment was done as a randomised, double-blind, crossover trial after an initial baseline study with vehicle (0.45% saline). Plasma potassium concentration, spirometry and the degree of breathlessness (Borg scale) were measured before treatment and immediately after exercise; oxygen saturation, QTc interval and cardiac rhythm were monitored continuously before, during and for 30 min after exercise. Results: After the saline control, exercise caused an increase in Borg rating (of 4.9), a premature ventricular contractions (VPC) (2.8 beats/min), and a fall in oxygen saturation (-6.7%), but no significant change in plasma potassium (+0.04 mEq · dl^-1), FEV₁ or QTc interval. Inhalation of fenoterol and salbutamol did not affect QTc interval, Borg scale or VPC frequency at rest, but significantly increased the duration of exercise undertaken to reach the submaximal levels (786 s, versus 783 s) compared to the vehicle control. Following exercise, plasma potassium fell after fenoterol by 0.2 mEq · dl^-1 and it increased after salbutamol by 0.1 mEq · dl^-1 compared to baseline levels. Plasma potassium after exercise was significantly lower after fenoterol (3.2 mEq · dl^-1) compared to the saline control (3.7 mEq · dl^-1) and salbutamol (3.6 mEq · dl^-1). Neither fenoterol nor salbutamol had any significant effect on the change in FEV₁, oxygen saturation, Borg scale, frequency of VPCs or QTc interval during or after exercise compared to the saline control. Conclusion: When compared to salbutamol 2 mg, fenoterol 2 mg caused more marked hypokalaemia but no significant difference in cardiopulmonary response in patients with COPD during exercise.