Clinical features of amiodarone-induced pulmonary toxicity

Raymond E. Dusman, Marshall S. Stanton, William M. Miles, Lawrence S. Klein, Douglas P. Zipes, Naomi S. Fineberg, James J. Heger

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Abstract

The incidence and clinical predictors of amiodarone pulmonary toxicity were examined in 573 patients treated with amiodarone for recurrent ventricular (456 patients) or supraventricular (117 patients) tachyarrhythmias. Amiodarone pulmonary toxicity was diagnosed in 33 of the 573 patients (5.8%), based on symptoms and new chest radiographic abnormalities (32 of 33 patients) and supported by abnormal pulmonary biopsy (13 of 14 patients), low pulmonary diffusion capacity (DLCO) (nine of 13 patients), and/or abnormal gallium lung scan (11 of 16 patients). Toxicity occurred between 6 days and 60 months of treatment for a cumulative risk of 9.1%, with the highest incidence occurring during the first 12 months (18 of 33 patients). Older patients developed it more frequently (62.7±1.7 versus 57.4±0.5 years,p=0.018), with no cases diagnosed in patients who started therapy at less than 40 years of age. Gender, underlying heart disease, arrhythmia, and pretreatment chest radiographic, spirometric, or lung volume abnormalities did not predict development of amiodarone pulmonary toxicity, whereas pretreatment DLCO was lower in the group developing it (76.0±5.5% versus 90.4±1.4%, p=0.01). There was a higher mean daily amiodarone maintenance dose in the pulmonary toxicity group (517±25 versus 409±6 mg, p<0.001) but no difference in loading dose. No patient receiving a mean daily maintenance dose less than 305 mg developed pulmonary toxicity. Patients who developed toxicity had higher plasma desethylamiodarone (2.34±0.18 versus 1.92±0.04 μg/ml, p=0.009) but not amiodarone concentrations during maintenance therapy. Death due to pulmonary toxicity occurred in three of 33 patients (9.1%). In conclusion: 1) amiodarone pulmonary toxicity occurred in 5.8% of patients and was more common with a higher amiodarone maintenance dose, advanced age, lower pretreatment DLCO, and higher plasma desethylamiodarone concentrations; and 2) pretreatment chest radiographic, spirometric, and lung volume abnormalities were not predictive for development of amiodarone pulmonary toxicity.

Original languageEnglish
Pages (from-to)51-59
Number of pages9
JournalCirculation
Volume82
Issue number1
StatePublished - 1990

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Amiodarone
Lung
Thorax
Lung Volume Measurements
Gallium
Incidence
Tachycardia

Keywords

  • Diffusion capacity
  • Drug side effect
  • Pneumonitis
  • Pulmonary fibrosis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Dusman, R. E., Stanton, M. S., Miles, W. M., Klein, L. S., Zipes, D. P., Fineberg, N. S., & Heger, J. J. (1990). Clinical features of amiodarone-induced pulmonary toxicity. Circulation, 82(1), 51-59.

Clinical features of amiodarone-induced pulmonary toxicity. / Dusman, Raymond E.; Stanton, Marshall S.; Miles, William M.; Klein, Lawrence S.; Zipes, Douglas P.; Fineberg, Naomi S.; Heger, James J.

In: Circulation, Vol. 82, No. 1, 1990, p. 51-59.

Research output: Contribution to journalArticle

Dusman, RE, Stanton, MS, Miles, WM, Klein, LS, Zipes, DP, Fineberg, NS & Heger, JJ 1990, 'Clinical features of amiodarone-induced pulmonary toxicity', Circulation, vol. 82, no. 1, pp. 51-59.
Dusman RE, Stanton MS, Miles WM, Klein LS, Zipes DP, Fineberg NS et al. Clinical features of amiodarone-induced pulmonary toxicity. Circulation. 1990;82(1):51-59.
Dusman, Raymond E. ; Stanton, Marshall S. ; Miles, William M. ; Klein, Lawrence S. ; Zipes, Douglas P. ; Fineberg, Naomi S. ; Heger, James J. / Clinical features of amiodarone-induced pulmonary toxicity. In: Circulation. 1990 ; Vol. 82, No. 1. pp. 51-59.
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abstract = "The incidence and clinical predictors of amiodarone pulmonary toxicity were examined in 573 patients treated with amiodarone for recurrent ventricular (456 patients) or supraventricular (117 patients) tachyarrhythmias. Amiodarone pulmonary toxicity was diagnosed in 33 of the 573 patients (5.8{\%}), based on symptoms and new chest radiographic abnormalities (32 of 33 patients) and supported by abnormal pulmonary biopsy (13 of 14 patients), low pulmonary diffusion capacity (DLCO) (nine of 13 patients), and/or abnormal gallium lung scan (11 of 16 patients). Toxicity occurred between 6 days and 60 months of treatment for a cumulative risk of 9.1{\%}, with the highest incidence occurring during the first 12 months (18 of 33 patients). Older patients developed it more frequently (62.7±1.7 versus 57.4±0.5 years,p=0.018), with no cases diagnosed in patients who started therapy at less than 40 years of age. Gender, underlying heart disease, arrhythmia, and pretreatment chest radiographic, spirometric, or lung volume abnormalities did not predict development of amiodarone pulmonary toxicity, whereas pretreatment DLCO was lower in the group developing it (76.0±5.5{\%} versus 90.4±1.4{\%}, p=0.01). There was a higher mean daily amiodarone maintenance dose in the pulmonary toxicity group (517±25 versus 409±6 mg, p<0.001) but no difference in loading dose. No patient receiving a mean daily maintenance dose less than 305 mg developed pulmonary toxicity. Patients who developed toxicity had higher plasma desethylamiodarone (2.34±0.18 versus 1.92±0.04 μg/ml, p=0.009) but not amiodarone concentrations during maintenance therapy. Death due to pulmonary toxicity occurred in three of 33 patients (9.1{\%}). In conclusion: 1) amiodarone pulmonary toxicity occurred in 5.8{\%} of patients and was more common with a higher amiodarone maintenance dose, advanced age, lower pretreatment DLCO, and higher plasma desethylamiodarone concentrations; and 2) pretreatment chest radiographic, spirometric, and lung volume abnormalities were not predictive for development of amiodarone pulmonary toxicity.",
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N2 - The incidence and clinical predictors of amiodarone pulmonary toxicity were examined in 573 patients treated with amiodarone for recurrent ventricular (456 patients) or supraventricular (117 patients) tachyarrhythmias. Amiodarone pulmonary toxicity was diagnosed in 33 of the 573 patients (5.8%), based on symptoms and new chest radiographic abnormalities (32 of 33 patients) and supported by abnormal pulmonary biopsy (13 of 14 patients), low pulmonary diffusion capacity (DLCO) (nine of 13 patients), and/or abnormal gallium lung scan (11 of 16 patients). Toxicity occurred between 6 days and 60 months of treatment for a cumulative risk of 9.1%, with the highest incidence occurring during the first 12 months (18 of 33 patients). Older patients developed it more frequently (62.7±1.7 versus 57.4±0.5 years,p=0.018), with no cases diagnosed in patients who started therapy at less than 40 years of age. Gender, underlying heart disease, arrhythmia, and pretreatment chest radiographic, spirometric, or lung volume abnormalities did not predict development of amiodarone pulmonary toxicity, whereas pretreatment DLCO was lower in the group developing it (76.0±5.5% versus 90.4±1.4%, p=0.01). There was a higher mean daily amiodarone maintenance dose in the pulmonary toxicity group (517±25 versus 409±6 mg, p<0.001) but no difference in loading dose. No patient receiving a mean daily maintenance dose less than 305 mg developed pulmonary toxicity. Patients who developed toxicity had higher plasma desethylamiodarone (2.34±0.18 versus 1.92±0.04 μg/ml, p=0.009) but not amiodarone concentrations during maintenance therapy. Death due to pulmonary toxicity occurred in three of 33 patients (9.1%). In conclusion: 1) amiodarone pulmonary toxicity occurred in 5.8% of patients and was more common with a higher amiodarone maintenance dose, advanced age, lower pretreatment DLCO, and higher plasma desethylamiodarone concentrations; and 2) pretreatment chest radiographic, spirometric, and lung volume abnormalities were not predictive for development of amiodarone pulmonary toxicity.

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