Influence of cardioselectivity and respiratory disease on pulmonary responsiveness to beta-blockade

The effects on ventilation of the non-selective beta-blocker propranolol, and the relatively cardioselective beta-blocker, metoprolol, were compared in a randomized single-blind crossover study in 16 patients with asthma, bronchitis and emphysema (American Thoracic Society criteria). Group I had "fixed" airways disease with less than 20% improvement in FEV1 following inhaled salbutamol 5 mg by nebuliser. Group II had "reversible" obstruction, greater than 20% improvement. Bronchodilator therapy was withheld for 24 h with the exception of aerosols which were permitted until 12 h before study. After control observations on each of 2 study days, each patient received cumulative doses of propranolol (maximum 170 mg) and metoprolol (maximum 187.5 mg). Ventilatory function (FEV1, FVC, FEV1%) was assessed at 0, 2, 4, 6 and 8 h. In Group I, 2 patients were unable to complete the study. One patient became dizzy with propranolol 70 mg but tolerated metoprolol 187.5 mg. One patient developed wheeze with propranolol 15 mg but tolerated metoprolol 187.5 mg. Metoprolol was tolerated in all 8 patients with "fixed" disease, although FEV1 was reduced by more than 30% in 1 patient. Three patients in Group II did not complete the study because of wheezing following propranolol 10 mg, metoprolol 37.5 mg; propranolol 17.5 mg, metoprolol 37.5 mg; propranolol 45 mg, tolerated metoprolol 187.5 mg respectively. Wheezing responded in all cases to inhaled isoprenaline. The response to either propranolol or metoprolol was unpredictable in patients with "reversible" disease. When wheezing occurred in this group, it developed following small, potentially subtherapeutic doses of each drug. Although metoprolol was better tolerated, the practical benefit of cardioselectivity in those patients with reversible airways disease was negligible.