Serial pulmonary function tests in patients treated with low-dose amiodarone

Problems with pulmonary toxicity have emerged as a potentially limiting factor for amiodarone use. We studied 24 consecutive patients receiving low-dose (i.e., less than or equal to 400 mg/day) amiodarone for refractory tachyarrhythmias. Serial pulmonary function test results were correlated with daily dose, serum concentration, cumulated dose, and duration of amiodarone treatment to determine the effect of the drug on pulmonary function. The mean follow-up period for the 24 patients, who completed baseline and follow-up evaluations, was 47 months (range 31 to 75 months). In 22 of the 24 patients a reduction in total diffusion capacity (TLCO) was noted after treatment; for all 24 patients the mean reduction in TLCO was 12.9% of the predicted value (SD 9.6% predicted) (p less than 0.02). The decrease in TLCO was found to be significantly related to an increasing cumulated dose of amiodarone (p = 0.007), whereas the reduction in TLCO was found to be unrelated to sex, age, underlying heart disease, arrhythmia, daily dose of amiodarone, duration of treatment, plasma concentration of amiodarone and desethylamiodarone, and pretreatment pulmonary function abnormalities. Seven (29%) of the patients had asymptomatic pulmonary toxicity with a decrease in TLCO greater than or equal to 20% of the predicted value. In conclusion, long-term treatment with low-dose amiodarone was associated with a substantial decrease in TLCO, a higher cumulative dose of the drug was related to an increasing reduction in TLCO, and pretreatment pulmonary function abnormalities were not predictive for development of subclinical pulmonary toxicity.