Amiodarone Pulmonary Toxicity: Assessment by Bronchoalveolar Lavage

doi:10.1378/chest.88.4.630

Chest

Volume 88, Issue 4, October 1985, Pages 630-631

https://doi.org/10.1378/chest.88.4.630 Get rights and content

Bronchoalveolar lavage was used to demonstrate morphologic changes in alveolar macrophages characteristic of amiodarone effect in lung tissue obtained by biopsy. This procedure may be useful in the assessment of abnormal chest x-ray findings in patients suspected to have amiodarone toxicity.

Section snippets

Case Report

A 56-year-old white man with a history of syncope due to recurrent ventricular tachycardia had received amiodarone for three years. Due to a recent increase in syncopal episodes, the dose of amiodarone was increased from 300 to 400 mg every day. Approximately two weeks later, the patient noted the onset of bilateral pleuritic chest pain. Physical examination revealed scattered rales at both bases. There was no evidence of congestive heart failure. The chest x-ray examination revealed bibasilar

Discussion

Amiodarone is an effective antiarrhythmic agent which is likely to be available for widespread clinical use in the near future. The major factor limiting its use is the risk of life-threatening pulmonary toxicity.1, 2, 3 Patients receiving amiodarone often have multiple reasons for abnormal chest x-ray findings including congestive heart failure, pulmonary infarction or respiratory infections. Lung biopsy specimens from both bronchoscopic and open surgical procedures have been utilized to

References (6)

F.E. Marchlinski et al.
Amiodarone pulmonary toxicity
Ann Intern Med
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W.B. Gefter et al.
Lung disease caused by amiodarone, a new antiarrhythmic agent
Radiology
(1983)
L. Rakita et al.
Amiodarone pulmonary toxicity
Am Heart J
(1983)

There are more references available in the full text version of this article.

Cited by (19)

Amiodarone toxicity in a patient with simultaneous involvement of cornea, thyroid gland, and lung
2000, American Journal of the Medical Sciences
Amiodarone, an iodine-rich benzofuran derivative, is a highly effective agent for the prophylaxis and treatment of cardiac arrhythmias, but it is associated with numerous side effects. Amiodarone toxicity involving several organs simultaneously has rarely been reported heretofore. In this report, we describe a case of a 73-year-old man who developed symptomatic hypothyroidism, pulmonary toxicity, and vortex epitheliopathy of the cornea during 6 months of amiodarone therapy for frequent palpitation and angina after myocardial infarction. This case illustrates that amiodarone may cause toxicity involving several organs concurrently in a patient receiving long-term amiodarone therapy. This may be of clinical significance in managing such patients.
Characterization of amiodarone pneumonitis as related to inflammatory cells and surfactant apoprotein
1997, Chest
To characterize the inflammation observed in amiodarone-induced pneumonitis.
The density of inflammatory cells in BAL fluid (BALF) and lung interstitium was quantified in a rat model of amiodarone pneumonitis. Immunoperoxidase staining for surfactant apoprotein was evaluated in lung tissue.
Male Fischer 344 rats weighing 170 to 180 g received amiodarone, 150 mg/kg/d, suspended in 0.5% methylcellulose by gavage 5 d/wk. Control animals were given only methylcellulose. Rats were killed after 3, 5, 7, 9, and 12 weeks. Histologic sections were prepared for hematoxylin-eosin staining and the immunoperoxidase method.
Significant positive correlations between the density of neutrophils in BALF and the interstitium were seen at 5 weeks (r=0.90, p<0.05) and 7 weeks (r=0.90, p<0.05). Significant positive correlations were observed between the density of lymphocytes in BALF and the interstitium at 9 weeks (r=0.90, p<0.05) and 12 weeks (r=0.90, p<0.05). The density of type II pneumocytes was significantly increased in the amiodarone-fed rats. Extracellular surfactant apoprotein was found in the alveolar space and the cytoplasm of type II pneumocytes, Clara cells, and large, foamy macrophages throughout drug treatment. Extracellular surfactant apoprotein filled some alveoli at 9 weeks.
The density of lymphocytes and neutrophils increased significantly in the BALF and the lung interstitium throughout amiodarone administration. The relationship between the density of lymphocytes in BALF and in the interstitium differed from that of neutrophils. In addition, amiodarone caused hyperplasia of type II pneumocytes and deposition of conglomerated, extracellular surfactant apoprotein in the alveolar space.
Bronchoalveolar lavage cell count and differential are not reliable indicators of amiodarone-induced pneumonitis
1992, Chest
Amiodarone-induced interstitial pneumonitis is a serious, frequently fatal untoward effect of a commonly used antiarrhythmic agent. Recent reports suggest that bronchoalveolar lavage (BAL) fluid cellular analysis might be used to diagnose amiodarone-induced pneumonitis. The purpose of this study was to determine if the diagnosis of amiodarone-induced pneumonitis could be made by patient history, pulmonary function evaluation, and examination of BAL fluid. We studied five groups of patients. Three of the five groups received amiodarone: patients receiving amiodarone without evident lung toxic reaction, patients with amiodarone-induced pneumonitis, and amiodarone-treated patients diagnosed as having other pathologic processes involving the lung. The two other groups examined were healthy volunteers and patients with interstitial lung disease from causes other than amiodarone. Pulmonary function tests included vital capacity (FVC), first second forced exhaled volume (FEV₁), total lung capacity (TLC), and diffusing capacity for carbon monoxide (DCO). BAL fluid analysis included total and differential cell counts. We found that amiodarone-induced interstitial pneumonitis was not associated with an alteration in pulmonary function or BAL cellular composition which could permit its distinction from amiodarone-treated patients diagnosed as having an unrelated pulmonary process or patients with interstitial lung disease from other causes. The most frequent abnormality encountered in patients with amiodarone toxicity was a reduction in the percentage of macrophages in the differential cell count. The sensitivity, specificity, and predictive value of this finding was 82 percent, 69 percent, and 69 percent, respectively. The sensitivity, specificity, and predictive value of a ≥15 percent reduction in DCO was 44 percent, 50 percent, and 36 percent, respectively. We conclude that amiodarone-induced interstitial pneumonitis remains a diagnosis of exclusion, and the role of BAL fluid analysis is to narrow the differential diagnosis through microbiologic culture and cytologic examination.
Southwestern Internal Medicine Conference: Amiodarone pulmonary toxicity
1992, American Journal of the Medical Sciences
Amiodarone is an effective antiarrhythmic agent whose utility is limited by many side-effects, the most problematic being pneumonitis. The pulmonary toxicity of amiodarone is thought to result from direct injury related to the intracellular accumulation of phospholipid and T cell-mediated hypersensitivity pneumonitis. The clinical and radiographic features of amiodarone-induced pulmonary toxicity are characteristic but nonspecific. The diagnosis depends on exclusion of other entities, such as heart failure, infection, and malignancy. While withdrawal of amiodarone leads to clinical improvement in majority of cases, this is not always possible or advisable. Dose reduction or concomitant steroid therapy may have a role in selected patients.
Bronchoalveolar lavage cell data in amiodarone-associated pneumonitis: Evaluation in 22 patients
1991, Chest
To assess the value of bronchoalveolar lavage (BAL) for diagnosis, understanding, and treatment of amiodarone-associated pneumonitis, we examined the results of BAL total and differential cell counts and phenotyping of lymphocytes in 22 patients with this lung disorder and in 33 normal subjects. Overall, the total cell count was found to be almost the same as that seen in control subjects; the macrophage population was significantly reduced, and the lymphocyte, neutrophil, and eosinophil populations were increased in absolute number and percentage. When results were analyzed individually, BAL data appeared to be distributed according to two patterns. In the first pattern, there was no abnormal lymphocytosis. In the second pattern a lymphocyte alveolitis was found in percentage and in absolute number. This lymphocyte alveolitis was present either alone or associated with neutrophil alveolitis or with eosinophil alveolitis. In the first pattern, despite the normal level of the lymphocyte population, the percentage of CD4 T-lymphocytes and the CD4:CD8 T-lymphocyte ratio were significantly lowered. In the second pattern the CD8 T-lymphocyte count was increased in absolute number and percentage, with a low CD4:CD8 ratio. In six patients relavaged two to four months after amiodarone withdrawal, there was a significant fall in alveolar lymphocytosis, but the progressive increase in the neutrophil population over time seemed to be associated with the seriousness and progression of the disease. Finally, these findings closely resembled those obtained in patients with hypersensitivity pneumonitis due to inhalation of organic dust and suggest that an underlying immunologic cell-mediated mechanism may play a role in this iatrogenic pulmonary disease. (Chest 1991; 99:1177-82)
A general overview of amiodarone toxicity: Its prevention, detection, and management
1989, Progress in Cardiovascular Diseases
Although amiodarone is a highly effective antiarrhythmic agent, it has a high incidence of side effects, some of which can be serious or even lethal. With close monitoring, side effects can be found in essentially all patients, but fortunately most of these are mild and well tolerated. Furthermore, many will respond to dosage reduction in a relatively short period of time, ie, days to weeks, which is remarkable considering the long period of time amiodarone has been shown to persist in tissues. There is reasonable evidence that toxicity, particularly the early toxic manifestations with large loading dosages, can be favorably modified by reducing the dosage. Similarly, reducing the maintenance dosage will, in most instances, reduce or eliminate most toxic manifestations. The mechanisms of toxic effects are uncertain, but suggestive evidence exists for and against both an immunologic reaction and an intracellular lysosomal lipoidosis.
Principles of use of amiodarone should include individualizing administration of dosages for each patient due to the unusual pharmacokinetic properties of this drug and continuous long-term attempts at using the lowest effective dosage. There are no definite tests that predict amiodarone efficacy or toxicity, but the serum level can be used as a rough guide of absorption and distribution in the attempt to minimize the maintenance dosage. No guidelines regarding screening tests for toxicity can be made at this time since great variability in these tests has been reported, and no evidence exists for their benefit in preventing adverse effects to amiodarone. However, follow-up testing at the intervals noted in the package insert are reasonable and important. The possibility of interactions with drugs already reported and with others not yet reported should always be kept in mind, and appropriate monitoring for clinical evidence of toxicity due to the concomitantly used drugs should be undertaken.
Amiodarone can have a tremendous beneficial effect in the proper circumstances, but it is a drug that should command utmost respect because of its side effects and requires constant vigilance from any physician wishing to use it.

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Chest

Selected ReportsAmiodarone Pulmonary Toxicity: Assessment by Bronchoalveolar Lavage

Section snippets

Case Report

Discussion

Amiodarone pulmonary toxicity

Ann Intern Med

Lung disease caused by amiodarone, a new antiarrhythmic agent

Radiology

Amiodarone pulmonary toxicity

Am Heart J

Selected Reports
Amiodarone Pulmonary Toxicity: Assessment by Bronchoalveolar Lavage