Usefulness of serial pulmonary function testing as an indicator of amiodarone toxicity

Abstract

A prospective study was conducted of 189 patients treated with amiodarone, maintained at doses of 400 to 800 mg/day and followed for up to 6 years. Only patients who had life-threatening ventricular arrhythmias unresponsive to conventional therapy were enrolled, and they underwent baseline pretreatment pulmonary function tests, with follow-up testing every 6 months. Morbidity and mortality statistics were confirmed by chart review and patient telephone interview. Of the 189 enrolled patients, 101 are alive, 84 are dead and 4 are lost to follow-up. Amiodarone-induced toxicity to the neurologic system, lungs, thyroid or liver was the primary or complicating cause of death in 12 of the 84 patients who died. The overall prevalence of all these forms of toxicity was 15%. Sixty-nine percent of the patients with amiodarone toxicity had pulmonary toxicity atone or combined with other forms of toxicity. Pulmonary function test abnormalities were noted at baseline in 75% of patients who had amiodarone-induced toxicity. The proportion of abnormal baseline pulmonary function tests was not significantly different among all toxic patients, pulmonary toxic patients and nontoxic patients. An evaluation of the decrease in pulmonary function over time could not distinguish patients who developed toxicity from those who did not. The observed incidence of pulmonary toxicity is consistent with published values; however, contrary to the findings of others, no statistically significant differences in pulmonary function at baseline or in changes over time were found between toxic and nontoxic patients. Differences from previous findings may be reflective of the more severe illness of the present population as evidenced by the high prevalence of abnormal pulmonary function at baseline and a high incidence of subsequent cardiac death. Two findings have not been previously reported: abnormal pulmonary function tests in patients with amiodarone-induced toxicity in nonpulmonary organs, and the frequent finding of concurrent multiple organ involvement in pulmonary toxic patients. The data indicate that pulmonary function tests are only a nonspecific indicator of pulmonary abnormalities in a population with preexisting cardropulmonary disease. In the absence of a specific diagnostic test, diagnosis of amiodarone pulmonary toxicity rests on a constellation of characteristics compiled from pulmonary function tests, chest x-rays, physical signs and a compatible history.