Difficulty Breathing: What could be contributing?

75 year old African American female with history of chronic heart failure (CHF), hypertension, atrial fibrillation with an implantable cardioverter-defibrillator (ICD), diabetes mellitus, asthma with chronic obstructive pulmonary disease (COPD), came to the ED with a chief complaint of “I woke up this morning and could not breathe”. The patient also had a cough with thick yellow and green phlegm, wheezing, and chest congestion. The patient reported worsening of the symptoms over the past couple of months with several admissions during this time for similar symptoms. The patient was treated with one nitroglycerin 0.4 mg SL tablet, furosemide 80mg IV, placed on CPAP, and given 2 doses of albuterol-ipratropium 3 ml nebulizer prior to arrival by EMS resulting in some improvement in symptoms. While in the hospital, the patient was started on metoprolol 50 mg tablet oral BID, enalapril 5mg tablet oral daily, amiodarone 400 mg BID, albuterol-ipratropium 3 ml nebulize every 6 hours, and fluticasone-salmeterol 250 mcg-50 mcg 1 puff BID. Patient’s vitals on arrival were: BP= 100/63, HR= 70 and RR= 18. Her chest X-ray showed diffuse interstitial, slightly nodular, opacities bilaterally and pulmonary venous congestion consistent with that observed during prior admissions.

Patient’s shortness of breath was diagnosed as CHF exacerbation. However, it is important to examine the patient profile closely to find possible underlying/contributing cause(s) of the symptoms. The patient was started on amiodarone 400 mg BID as a loading dose a year and a half ago for paroxysmal atrial fibrillation with rapid ventricular response (RVR). Prior to beginning of amiodarone, cardioversion was attempted. The plan was to wean the dose of amiodarone to 200mg TID for 1 week and then 200mg BID. However, patient’s dose was not re-evaluated and was continued at 400 mg BID. In this case, one of the possible contributing factors to the patient’s worsening pulmonary function could be prolonged use of amiodarone at a high dose.

One of the most serious, potentially life threatening adverse reaction of amiodarone is pulmonary toxicity; it is one of the leading causes for discontinuation of the drug. Some of the common pulmonary manifestations of amiodarone-induced pulmonary toxicity (AIPT) are interstitial pneumonitis, organizing pneumonia, eosinophilic pneumonia, acute respiratory distress syndrome (ARDS), pulmonary fibrosis, diffuse alveolar hemorrhage, pleural effusion. Risk factors for AIPT are uncertain but, may include a high cumulative dose, daily dose greater than 400 mg/day, duration of therapy exceeding two months, increased patient age (> 60 years), pre-existing lung disease, thoracic or non-thoracic surgery, and pulmonary angiography. The prevalence of AIPT is estimated to be about 5-7%. Two major hypotheses of AIPT include a direct toxic injury to lung cells and an indirect immunologic reaction. Due to the frequency and potential severity of AIPT, early detection is desirable. Patients who may benefit from amiodarone should be carefully selected and the lowest effective dosage of amiodarone should be administered. Treatment of AIPT consists primarily of stopping amiodarone and, in most patients, initiating systemic glucocorticoids at the dose equivalent to oral prednisone 40 to 60 mg/day. Patients with mild symptoms (dyspnea on mild to moderate exertion) and normal oxygenation can be observed off amiodarone without glucocorticoids.  References

Submitted By:

Chandni Dudhia, PharmD-PGY 1 Pharmacy Practice Resident in collaboration with Donna M. Lisi, PharmD, BCPS, BCPP, Barnabas Health Care System, South Plainfield, NJ


  1. Mike Recktenwald

    I’m curious as to the reson why the amiodarone wasn’t d/c’d after the implantable device was placed for the same purpose. I also question the statement that she had been admitted several times previous to this and no pharmacological changes were made then. I appreciate the admit vitals, but where is her medication list? It appears that there is a lot of work to be done on her behalf to try and give her some quality of life before she looses that window of opportunity.

    • Chandni Dudhia

      Hi Mike,
      Thank you for your response. This patient came in to the ER a year and a half ago with ICD already placed and still having atrial fibrillation with RVR. The patient was then started on amiodarone. I definitely agree that pharmacological changes should have been made during prior admissions. The main idea of this post is to point out 2 things: 1) Lack of appropriate medication management and its possible consequences and 2) Patient’s symptoms possibly due to amiodarone toxicity. The patient was started on loading dose of amiodarone and the dose was never re-evaluated again. The documented list of home medications during patient’s recent admission was as follows:

      Advair 250mcg-50mcg INH: 1 Puff, Inhalation, 2 times a Day Resp
      Flonase 50 mcg/inh nasal spray: 1 Spray, Nasal, Daily
      amiodarone 200 mg oral tablet: 2 Tab, Oral, Every 12 Hr
      cyclobenzaprine 10 mg oral tablet: 1 Tab, Oral, Daily
      docusate sodium 100 mg oral capsule: 1 Cap, Oral, 2 times a Day, PRN Constipation
      enalapril 2.5 mg oral tablet: 2 Tab, Oral, Daily
      furosemide 40 mg oral tablet: 1 Tab, Oral, Daily
      glipiZIDE 10 mg oral tablet: 1 Tab, Oral, 2 times a Day
      metoprolol tartrate 50 mg oral tablet: 1 Tab, Oral, Every 12 Hr
      pregabalin 75 mg oral capsule: 1 Cap, Oral, 2 times a Day
      sitaGLIPtin 25 mg oral tablet: 1 Tab, Oral, Before Breakfast

  2. Mary Butcher

    Excellent post!

  3. koyakuttymeletath

    A very good information Amiodarone dose related toxicity

  4. koyakuttymeletath

    A very good example for amiodarone dose related toxicity

  5. Bill Jones

    It is not just the dose being re-evaluated. The response MUST be re-evaluated. If the patient was still having paroxysmal A-Fib, why should amiodarone be continued at all? Stopping ineffective therapy and not just dose adjustment must be part of the plan. This could be a common problem. Several times a cardiolologist would tell me they were using amiodarone for rate control when it failed to work. Already giving metoprolol, so is another beta-blocking drug needed?

    • Chandni Dudhia

      Hi Bill,
      Thank you for your comment. The patient had history of paroxysmal A-fib for which the patient came into the ED a year and a half ago. At that point, the patient was started on a loading dose of amiodarone and the dose was not re-evaluated. I agree with the point that the patient’s need for amiodarone therapy should have been re-evaluated based on her response before continuing the medication. However, her most recent admissions were all because of her symptoms of shortness of breath and not atrial fibrillation. Based on patient’s latest EKG, patient had normal sinus rate and rhythm on the combination of amiodarone and metoprolol. When I consulted patient’s cardiologist, he wanted to continue amiodarone and was unaware that patient’s amidorone dose was as high as 400 mg BID. He agreed to reduce the dose to 200 mg BID.

      • chri1599

        Good discussion! Thanks Chandni for the case!

      • Bill Jones


        I would add two other points. These are not meant to be criticism, but food for thought to other thoughts.

        First, medicine has become too much focused on things and not patients. Just because the patient was admitted for shortness of breath and not atrial fibrillation does not mean atrial fibrillation should be ignored. I watched this evolution over nearly 30 years of being on the wards. It is almost like the inpatient team says “It is not my job to do anything about AF, since he is here for SOB.”

        Second, if getting amiodarone 400 mg BID and STILL going into AF, the drug FAILED TO WORK. That is a compelling reason to stop it. Pulmonary toxicity should come to mind for ANYONE getting amiodarone regardless of the dose, and that should also have been a compelling reason to stop the drug. Rate control is acceptable and equal to rhythm control.

        Cardiologists can want to do things and be wrong at the same time. Is the cardiologist the PRIMARY physician or a consultant? One cardiologist I worked with a decades would say “Frequently wrong, but never in doubt”.

        This is as much about an amiodarone toxicity case as an amiodarone dosing case.

        A slightly different patient I saw a long time ago was admitted for syncope. The medical resident presented the patient quickly in morning report and could not remember all the drugs (there were so many). The “theme” was the patient was not interesting. I got his med list and he was getting 20 drugs. One was amiodarone and another was warfarin. Asking why he he getting amio? “He has A Fib.” Why is he getting warfarin? “He has A Fib. When asking if one of them did not fit, the answer was no. Turns out the patient had been in NSR for about 6 months after starting amiodarone, and no one stopped his warfarin. That was how it should be done. Oh, he had Hb about 9 g/dl, but someone said he “needed” warfarin. REALLY? Why is he anemic? Do you think warfarin is associated with bleeding? Do you continue warfarin when the patient is bleeding? Should you evaluate if someone has anemia (because it is never normal to be anemic).


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Written By Eric Christianson

April 5, 2015

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