INTRODUCTION:
Amiodarone, a class III antiarrhythmic drug is an iodinated benzofuran derivate used as a potent agent for the prevention and treatment of life-threatening ventricular and supraventricular arrhythmias.[1]
Its iodine-containing compound gives amiodarone the tendency to build up in various organs, such as the lungs. Although many adverse reactions and side effects of amiodarone have been reported, pulmonary toxicity and pneumonitis could perhaps be one of the critical adverse effects.[2]
Amiodarone is metabolized in the liver by cytochrome P-450 enzyme and is then excreted through the biliary system and is not dialyzable in case of overdose. Risk factors for amiodarone pulmonary toxicity consist of the male gender, age, preexisting pulmonary diseases, high oxygen demand conditions, thoracic surgery, and pulmonary angiography.
The most common forms of amiodarone pulmonary toxicity are interstitial pneumonitis and organizing pneumonia but it can also present itself as a lung mass or a consolidation.
Amiodarone Pneumonitis usually manifests itself with non-specific respiratory symptoms such as cough, shortness of breath, myalgia, and fever.[3]
Due to these indefinite presentations, Amiodarone Pneumonitis is mostly diagnosed after excluding other differential diagnoses.
Amiodarone pulmonary toxicity is mostly delayed and occurs in higher accumulative dosages, in this case despite most reported cases, we report challenging early amiodarone-associated pneumonitis.[4]
Case presentation :
A 50-year-old heavy ex-smoker man with a past medical history of hyperlipidemia and hypertension was brought to the emergency department because of recent complaints of chest pain, sweating, nausea, and progressive dyspnea.
The initial physical examination showed a body temperature of 37.5°C, blood pressure of 96/70 mm Hg, pulse rate of 95 beats/minute, respiratory rate of 26 breaths/minute, and oxygen saturation of 90% while the patient was breathing without supplemental oxygen.
He also had bilateral crackles in auscultation, especially in the right lung, Other physical exam findings were unremarkable.
Immediately ECG and portable Chest x-ray were obtained which demonstrate ST segment elevation in precordial leads and bat wing pattern in CXR in favor of pulmonary edema. (figure1)
In less than 15 minutes the patient was sent to a catheterization laboratory and angiographic imaging revealed total occlusion of the left main artery.
Primary percutaneous catheter intervention and stenting on LAD and plain old balloon angioplasty (POBA) on the ramus intermedius artery were performed.
During the intervention he received, 150 mg amiodarone IV bolus in 10 minutes, 200 mg bolus of furosemide, heparin 12500 U, ondansetron 4 mg, epinephrine infusion 2 mcg /kg/min,
After the patient was sent to the critical care unit he experienced recurrent ventricular tachycardia episodes which 360 mg amiodarone over the next 6 hours, then 540 mg over the remaining 18 hours administered.
Other medications such as IV furosemide 40 mg twice a day, Dobutamine infusion ( 5 mg/hr and 5 mcg/kg/min respectively ) and oral spironolactone ( 25 mg twice a day), aspirin( 80 mg daily) Clopidogrel (75 mg daily ) and ivabradine (5 mg daily) were administered.
The next day patient’s dyspnea gradually improved and amiodarone(200mg BID) and furosemide(40 mg BID) changed to the oral form.
An Echocardiography was performed and an Ejection fraction of 20 %, Pulmonary artery pressure:45 mm Hg, severe left ventricular hypertrophy, diastolic dysfunction of grade 3, normal right ventricle size, antro-septal and apex akinesia, without significant valvular abnormality ,and pericardial effusion were reported.
Patient’s general condition was improving however on the seventh day of admission the patient developed worsening dyspnea, fever, and nonproductive cough.
Routine biochemistry, CBC diff, CKMb, blood culture, procalcitonin, autoimmune profiles, ESR, CRP, COVID-19 PCR, and Sputum culture samples were obtained and empirical antibiotics ( levofloxacin 750 mg daily, ceftriaxone 1 gr BID) administered and furosemide dosage was increased.
The ECG did not reveal any new changes.
Follow-up chest radiography was requested which demonstrated bilateral interstitial infiltrations. (figure 2)
Laboratory results showed: WBC 14.8 K/μL, Hgb 11 g/dL, PLT count 250 000 cell/mm3, MCV 90.6 fL, neutrophil 70.9%, lymphocyte 27.2%,Eosinophil :1% , CRP:42.7 mg/L, Urea 46 mg/dL, Cr 1.4 mg/dL, blood and sputum culture:negative, procalcitonin: negative , CKMb: negative , COVID-19 PCR (two times with the interval of 48 hours) :negative, ANA: negative , Complements: normal
Spiral chest computed tomography was requested which showed bilateral diffuse consolidations and ground glass opacities. (Figure 3)
First of all with the diagnosis of pulmonary edema and diuretic resistance high dose of furosemide in combination with Indapamide, hydrochlorothiazide, and metolazone was subsequently administered but no improvement was seen.
The echocardiography after the worsening of the symptoms demonstrated no change in Left Ventricle dysfunction and ejection fraction but an increase in pulmonary arterial pressure (PAP) to 60 mm Hg which after ruling out the pulmonary emboli the PAP increase was compatible with lung parenchymal involvement.
Due to the worsening of symptoms despite high dose diuretic, broad-spectrum antibiotic treatment and negative laboratory results for both viral and bacterial pneumonia and the CT scan consistent with interstitial pneumonitis, amiodarone-related interstitial pneumonitis was highly suspected and the patient candidate for bronchoalveolar lavage (BAL) and dexamethasone 8 mg IV daily started.
Despite the withdrawal of amiodarone his condition rapidly deteriorated within three days and suffered respiratory and kidney failure and cardiac arrest during hemodialysis. He underwent cardiorespiratory resuscitation for over 45 min, but could not be resuscitated and unfortunately died.