When Antibiotics, Diuresis and Steroids Are Not Enough - A Fatal Case of Amiodarone-Induced Pulmonary Toxicity

A 74-year-old man with hypertension, chronic kidney disease, coronary artery disease, chronic systolic heart failure and prior cardiac arrest due to ventricular tachycardia status-post implantable cardioverter-defibrillator placement presented to the emergency department with worsening dyspnea. He reported shortness of breath with exertion and dry nonproductive cough which had gradually progressed over the past several months. He reported compliance with home medications although could not specify which medications he was taking. He previously worked as a plumber, without known environmental exposures, sick contact, travel or extensive tobacco use. Physical exam revealed diffuse crackles in the bilateral posterior lung fields, jugular venous distension and pitting bilateral lower extremity edema. Due to suspicion for community acquired pneumonia and acute on chronic heart failure exacerbation, he was admitted to the hospital for intravenous (IV) antibiotics and diuresis. Transthoracic echocardiogram showed a reduced left ventricular ejection fraction and elevated pulmonary artery pressures, otherwise no valvulopathy, shunting or right ventricular dysfunction. His fluid status improved, although his oxygen requirements continued to rise. He was escalated from high flow nasal cannula to bilevel positive airway pressure ventilation, and transferred to the medical intensive care unit. Computed tomography pulmonary angiogram revealed no evidence of pulmonary embolism, although was significant for bilateral diffuse ground glass opacities with septal thickening, honeycombing and traction bronchiectasis. Respiratory viral panel, COVID-19 testing, fungal serologies and autoimmune/vasculitis workup were negative. Outside records consisted of recent diagnostic bronchoscopy which yielded unremarkable cytology and cultures, pulmonary function tests demonstrating restrictive lung pattern and severely reduced diffusion capacity of carbon monoxide, and normal ventilation-perfusion scan. Calls were placed to outside providers who confirmed that the patient had been on high-dose amiodarone (400 mg twice daily) for over the past decade, as previous attempts transition down or off amiodarone had led to his prior cardiac arrest. After discussion in multidisciplinary conferences, the patient was started on high-dose IV steroids due to suspicion for amiodarone-induced pulmonary toxicity (AIPT). Unfortunately, he decompensated further, and his family ultimately pursued hospice care. While the incidence of AIPT is less than 10-15%, this case serves a reminder of the potentially fatal pulmonary adverse events associated with amiodarone use, and emphasizes upon the essential need for close multiorgan monitoring while on the medication. There remains a strong demand for further research to elucidate dose-dependent and duration-dependent relationships between amiodarone use and associated pulmonary toxicity, as well as identifying predisposing risk factors.