Pulmonary Adverse Effects

Classical Amiodarone Pneumonitis (see Pneumonia, Interstitial Lung Disease-Etiology, and Cryptogenic Organizing Pneumonia)

• Epidemiology
  • Occurs in 6% of amiodarone-treated patients
  • Most cases of pulmonary toxicity occur in men (but this may be due to increased prevalence of use in men)
  • Amiodarone lung toxicity may occur more readily in those with previously abnormal lung function and/or CXR
  • Dose-Relationship of Lung Toxicity
    • Most patients who develop lung toxicity have been taking the drug for at least a month (and some for a few years)
    • Most patients who develop lung toxicity are taking at least 400 mg/day (number of case reports of toxicity with doses of 200 mg/day): there are case reports of patients taking 200 mg/day for years with no toxicity until dose is increased to 400 mg/day
    • However, lung toxicity does not correlate with serum levels of amiodarone
• Diagnosis
  • ABG: hypoxemia
  • PFT’s: restriction with decreased DLCO
  • Gallium Scan: positive in amiodarone pulmonary toxicity (due to inflammation), but negative in congestive heart failure
  • FOB: presence of foamy macrophages on BAL or TBB only confirms exposure to amiodarone, but does not indicate toxicity (importantly, absence of foamy macrophages rules out toxicity)
  • Open Lung Biopsy: may be necessary in some cases
    • BO: may be seen in cases with confluent lesions
    • BOOP: seen in some cases
    • Chronic Interstitial Pneumonia (with or without fibrosis)
    • Desquamative Interstitial Pneumonia (DIP)
    • Lymphocytic Interstitial Pneumonitis (LIP)
    • Phospholipidosis
      • Foamy macrophages: nonspecific finding (can be seen with use of chlorphentermine, neuroleptics, antidepressants, inhibitors of cholesterol synthesis as well as in lipid storage diseases, and a variety of other conditions in which the lung is injured such as ARDS and obstructive pneumonia) -> however, the absence of foamy macropahges eliminates the diagnosis
      • Type II pneumocytes with lamellar inclusions
    • Diffuse Alveolar Damage: some cases
    • Acute Necrotizing Pneumonia: some cases
    • Organizing Pneumonia (see Cryptogenic Organizing Pneumonia, [[Cryptogenic Organizing Pneumonia]]): some cases
    • Diffuse Alveolar Hemorrhage (see Diffuse Alveolar Hemorrhage, [[Diffuse Alveolar Hemorrhage]]): rare cases
  • CXR/Chest CT
    • Early in Course: interstitial, alveolar, or mixed alveolar-interstitial infiltrates
    • Focal or diffuse, asymmetric, upper lobe predominance (may mimic infiltrates of TB)
      • May be peripheral, mimicking the infiltrates of chronic eosinophilic pneumonia
      • Pleural effusion is uncommon
    • Later in Course: infiltrates progress and may coalesce with continued use
  • CBC: normal-mild leukocytosis with usually absent eosinophilia
    • However, some cases have eosinophilia, producing a pumonary infiltrates with eosinophilia-like picture
  • ESR: elevated (may decrease with drug withdrawal, supporting diagnosis of amiodarone lung toxicity)
  • ANA: negative
• Clinical
  • Insidious Onset Presentation (80% of cases)
    • Insidious Onset of Dyspnea
    • Non-Productive Cough
    • Low-Grade Fever (without chills)
    • Pleuritic Chest Pain (10% of patients)
    • Crackles
    • Absence of Clubbing
  • Acute Pneumonia-Like Presentation (20% of cases)
• Treatment
  • Withdrawal of amiodarone + corticosteroids (for at least 2-6+ months): most respond, but response is variable
  • Follow ESR: typically decreases with amiodarone withdrawal
• Prognosis: fatal in 5-10% of cases

Hyperdense or Mass-Like Consolidation (see Lung Nodule or Mass and Cryptogenic Organizing Pneumonia)

• Epidemiology: uncommon
• Diagnosis
  • CXR/Chest CT
    • Confluent infiltrate or nodule or mass: may cavitate
    • Chest CT is useful: amiodarone is iodinated and infiltrate will appear denser than surrounding soft tissue in the chest wall
• Pathology: cryptogenic organizing pneumonia
• Treatment/Prognosis: withdraw amiodarone -> complete resolution may take 2-12 months

Acute Lung Injury-ARDS (see Acute Lung Injury-ARDS)

• Epidemiology: uncommon -> occurs in post-operative setting, 18-72 hrs after surgery
• Physiology: may be related to high FIO2 administration during and/or after the procedure

Diffuse Alveolar Hemorrhage (see Diffuse Alveolar Hemorrhage)

• Epidemiology: rare (only a few reported cases of amiodarone-associated diffuse alveolar hemorrhage)
• Physiology: diffuse alveolar damage
• Pathology: bland alveolar hemorrhage (absence of pulmonary capillaritis)

Pleural Effusion (see Pleural Effusion-Exudate)

• Diagnosis: exudative (PMN, macrophage, or lymphocyte-predominant)

Cardiac Adverse Effects

• Bradycardia (see Bradycardia)
• Conduction Disturbances
• Hypotension (see Hypotension)
• Negative Inotropy
• Postural Hypotension due to Dysautonomia
• Potential for Alteration of Metabolism of Other Drugs
  • Digoxin
  • Coumadin
  • Phenytoin
  • Procainamide
  • Quinidine
• Proarrhythmic Effects
• QT Prolongation/Torsade (see Torsade): definite association with torsade

Gastrointestinal Adverse Effects

• Anorexia
• Nausea and Vomiting (see Nausea and Vomiting)

Hematologic Adverse Effects

• Bone Marrow Suppression

Hepatic Adverse Effects

• Asymptomatic Abnormal Liver Function Tests (LFT’s): appears to be associated with serum amiodarone levels
• Granulomatous Hepatitis
• Hepatic Nodules

Neuromuscular Adverse Effects

• Extrapyramidal Manifestations
• Peripheral Neuropathy (see Peripheral Neuropathy): appears to be associated with serum amiodarone levels
• Postural Hypotension due to Dysautonomia
• Proximal Muscle Weakness
• Sleep Disturbances: vivid dreams, nightmares, and sleeplessness

Ocular Adverse Effects

• Corneal Microdeposits: 100% of cases
• Halo Vision

Thyroid Adverse Effects

• Hyperthyroidism (see Hyperthyroidism): due to iodinated amiodarone
• Hypothyroidism (see Hypothyroidism): due to iodinated amiodarone

Skin Adverse Effects

• Bluish Discoloration of Skin
• Photodermatitis