ARRHYTHMOGENIC EFFECTS OF COMBINED ORALLY-ADMINISTERED THEOPHYLLINE AND ALBUTEROL IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY-DISEASE

1. Studies in asthmatic subjects have reported conflicting results abo ut the arrhythmogenic effects of beta agonist and theophylline. The pu rpose of the present study was to evaluate the effects of the combinat ion of these drugs in patients with chronic obstructive pulmonary dise ase (COPD). 2. Twelve COPD patients (FEV(1) = 1.2 +/- 0.3 L; PaO2 = 65 .7 +/- 9.0 mmHg) were evaluated by 24-h Holter monitoring on three dif ferent days. The first evaluation was done after the patient had been without any treatment for at least 24 h, the second after sustained-re lease theophylline for one week and the third after oral beta agonist (albuterol) and theophylline for one week. 3. Mean serum level of theo phylline was 1.9, 15.6 and 11.7 mu g/ml, and mean heart rate was 78.3, 82.0 and 84.5 beats/min for the first, second and third period, respe ctively. Four patients showed more than 10 premature atrial contractio ns/h in the baseline Holter, and this rate did not increase after eith er treatment. Three patients had more than 10 premature ventricular co ntractions/h (PVC) at baseline, with no increase while receiving theop hylline or the combination of theophylline and albuterol. However, one patient did have worsening of the arrhythmia while taking both drugs. There were 5 single PVCs/h at baseline and 150 single and 9 coupled P VCs/h plus 1 episode of non-sustained ventricular tachycardia during c ombined therapy. 4. We conclude that the combination of theophylline a nd a beta agonist (albuterol) may increase the premature ventricular c ontraction rate and the complexity of ectopic activity in COPD patient s.