Prospective Evaluation of Amiodarone Pulmonary Toxicity

doi:10.1378/chest.86.4.541

Chest

Volume 86, Issue 4, October 1984, Pages 541-548

https://doi.org/10.1378/chest.86.4.541 Get rights and content

Reports of pulmonary infiltrates in patients taking amiodarone, initiated the study of 69 patients for pulmonary toxicity using serial chest roentgenograms (CXRs), pulmonary function tests (PFTs), and symptoms before and during therapy. Mean PFTs did not significantly change from their baseline normal values, but 10 percent of patients had a ≤15 percent fall in total lung capacity, and 28 percent a ≤15 percent fall in diffusion capacity (Dco) following treatment. Initial abnormalities in pulmonary function or CXR were predictive of risk of developing pulmonary toxicity. Degree of exposure to amiodarone (dose plus duration) correlated only weakly with development of pulmonary toxicity, which could occur in patients taking relatively small doses of the drug. Pulmonary complications of amiodarone are common, in most cases reversible, and often confused with congestive heart failure or pneumonia. Patients should be evaluated before treatment by assessing symptoms, CXRs, and Dco. Patients with initial abnormalities in these parameters, particularly both CXR and Dco abnormalities, should be considered for alternative therapy.

Section snippets

Population

One hundred consecutive patients treated with amiodarone were studied (79 men, 21 women), from 31 to 79 years of age (mean 59 years). These patients were referred to the Center for Arrhythmia and Pre-Hospital Care at Harborview Medical Center for evaluation and treatment of refractory arrhythmias. Informed consent was obtained in all cases, and the study approved by the Human Subjects Research Committee at the University of Washington. Sixty-six of these 100 patients had ischemic heart disease

Baseline Characteristics and Group Trends

Thirty-two of the 69 amiodarone-treated patients (46 percent) had pre-existing obstructive lung disease, as defined by FEV₁/FVC of less than 75 percent (mean FEV₁/FVC [± SD]: 64 ± 14 percent). Twelve patients (17 percent) had a mild restrictive defect, defined as an initial total lung capacity (TLC) of less than 80 percent of predicted (mean TLC: 73 ± 5 percent of predicted), and 26 patients (38 percent) had a diffusion capacity abnormality defined by an initial Dco of less than 80 percent of

DISCUSSION

This study indicates that pulmonary complications of amiodarone are common, protean, and potentially severe. Two patients (3 percent) died of pulmonary complications, their deaths related directly or indirectly to amiodarone. Thirteen percent of patients treated with amiodarone developed new or worsening pulmonary interstitial infiltrates on chest roentgenogram, 55 percent of whom also had worsening pulmonary symptoms. In contrast, among patients in the mexiletine clinical comparison population

ACKNOWLEDCMENT

Connie K. Carman, B.S., provided technical assistance.

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Initial characteristics and outcome of hospitalized patients with amiodarone pulmonary toxicity
2014, Respiratory Medicine
Citation Excerpt :
Angiotensin system antagonist (ASA) treatment had been prescribed significantly more in the survival group (p = 0.042, HR 0.34 (95% CI 0.12–0.96)) (Fig. 2). Clinical features did not differ between the two groups (fever, asthenia, chest pain, cough, sputum, hemoptysis), except that symptoms occurred earlier (3 weeks [1,21] versus 7 weeks [3; 42], p = 0.003) and dyspnea was more severe (p = 0.007) in the non-survival group. Apart from a lower PaO2/FiO2 ratio in the non-survival group (p = 0.024), no other biological data were predictive of mortality.
Amiodarone-induced pulmonary toxicity (APT) is a serious adverse event that can lead to death. The aims of our study are to determine factors associated with mortality and to describe outcome and sequelae of patients with APT.
Forty-six patients with APT were divided into two groups according to survival at day 90 for a clinical, functional, biological and radiological comparaison. We then evaluated the evolution of 15 survivors at a median of three months [1–6 months] and/or 12 months [8–36 months].
Mortality of APT at day 90 was 37% (17 patients) and was linked to the speed of onset of symptoms and a high HRCT alveolar score. Angiotensin system antagonist treatment was prescribed significantly more in the survival group (p = 0.042, HR 0.34 (95% CI 0.12–0.96)). In surviving patients, dyspnea, vital capacity and HRCT alveolar score improved significantly while HRCT fibrosis score deteriorated gradually during the first six months. At the end of the study, all the surviving patients presented functional and/or radiological sequelae.
Severity of APT is linked to the extent and speed of onset of pulmonary damage. After the initial episode, the patients who survived improved slowly but with persistent sequelae.
Amiodarone-induced pulmonary toxicity: Case study with syndrome analysis
2013, Heart and Lung: Journal of Acute and Critical Care
Citation Excerpt :
Meticulous care is advisable in ensuring that steroids are not tapered too quickly, as fatal rebound toxicity has been noted after overly aggressive weaning.37 Slow improvement, over a course of as long as three38 to six39 months can be noted if the condition is addressed early in its course. Either delayed treatment or refractory cases may result in permanent pulmonary fibrosis40 or death.41
Amiodarone is often prescribed for the control of atrial and ventricular arrhythmias. While generally effective, the potential for a variety of side effects is substantial. Pulmonary toxicity, leading to acute or chronic respiratory failure, manifests with cough, dyspnea, infiltrates on chest radiograph, and a potential for progression to death. Although routinely cited as an adverse effect of amiodarone, it is relatively rare in terms of statistical incidence. In an effort to shed light on this syndrome, we present a stereotypical case study in amiodarone-induced pulmonary toxicity, as a prelude to a review of theorized pathophysiology, epidemiology, clinical presentation, diagnosis, therapeutics, monitoring recommendations, and areas for future research.
Smoking history and underlying lung disease are associated with poor outcome in patients developing interstitial pneumonia during low-dose amiodarone therapy
2013, Journal of Arrhythmia
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It has been suggested that an immunologic reaction may also produce a hypersensitivity response [22]. Some studies have suggested that preexisting lung disease might predispose the patient to lung toxicity [12,27], even though this has not been verified by other studies [25,28]. We also showed that patients with COPD had a higher relapse rate and poor prognosis.
Amiodarone is a useful antiarrhythmic drug, especially in patients with serious heart diseases, but amiodarone-induced interstitial pneumonia (AMD-IP) is sometimes lethal.
We retrospectively analyzed the clinical characteristics of 280 patients who were treated with daily oral amiodarone. Among the patients, 29 (10.2%) developed AMD-IP during the follow-up period of 66.0±38.2 months. The average dose of amiodarone in the AMD-IP group (173±10 mg) was significantly higher than that in the non-AMD-IP group (150±3 mg). The prevalence of smoking history (AMD-IP group: 70.0%; non-AMD-IP group: 42.2%; P<0.01) and underlying lung disease (AMD-IP group: 17.2%; non-AMD-IP group: 5.6%; P<0.05) was significantly higher in the AMD-IP group than in the non-AMD-IP group. Furthermore, multiple stepwise logistic regression analysis demonstrated that smoking history was an independent predictor of AMD-IP (OR, 3.56; 95% CI, 1.08–10.23; P<0.001). Among patients who developed AMD-IP, those with chronic obstructive pulmonary disease (COPD) had a higher relapse rate and a worse prognosis.
During the mean follow-up period of >5 years, 10.2% of patients receiving low-dose amiodarone therapy developed AMD-IP. Higher maintenance doses, smoking history, and preexisting lung disease were related to the development of AMD-IP. The AMD-IP patients with COPD had a poor prognosis.
Amiodarone pulmonary toxicity
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Pulmonary mass and multiple lung nodules mimicking a lung neoplasm as amiodarone-induced pulmonary toxicity
2001, European Journal of Internal Medicine
Amiodarone is an effective anti-arrhythmic agent. However, during long-term therapy, patients can develop severe adverse pulmonary reactions that are potentially life-threatening. A case of amiodarone-induced pulmonary toxicity is presented in a 78-year-old woman. She developed dyspnea and a pulmonary mass with associated multiple lung nodules mimicking a lung cancer following 5 years of treatment with amiodarone for atrial fibrillation. After drug withdrawal, and without any additional treatment, clinical and radiological improvement was observed, and radiological findings resolved completely within 6 months.
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.

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: Manuscript received revision accepted May 3.

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Chest

Prospective Evaluation of Amiodarone Pulmonary Toxicity

Section snippets

Population

Baseline Characteristics and Group Trends

DISCUSSION

ACKNOWLEDCMENT

Am Heart J

Am J Cardiol

Am J Cardiol

Am J Cardiol

Am Heart J

Am J Cardiol

Am Heart J

Am J Cardiol

Long-term management of sustained, recurrent, symptomatic ventricular tachycardia with amiodarone

Circulation

Electrophysiological assessment of amiodarone in treatment of resistant supraventricular arrhythmias

Br Heart J

Amiodarone keratopathy: drug-induced lipid storage disease

Arch Ophthalmol

Effect of amiodarone on serum triiodothyronine, reverse triiodothyronine, thyroxine and thyrotropin: a drug influencing peripheral metabolism of thyroid hormones

J Clin Invest

A peculiar cutaneous pigmentation from cordarone

Dermatologica

Pseudocyanotic pigmentation of the skin induced by amiodarone: a light and electron microscopic study

Can Med Assoc J