Asian Cardiovasc Thorac Ann 2007;15:e66-e68
© 2007 Asia Publishing EXchange Ltd
Acute Fatal Post-CABG Low Dose Amiodarone Lung Toxicity
Mihalis Argyriou, MD,
Panagiotis Hountis, MD,
Nicolaos Antonopoulos, MD,
Maria Mathioudaki, MD1
Cardiac Surgery Department
1 Pathology Department, Evaggelismos General Hospital Athens, Greece
For reprint information contact: Panagiotis Hountis, MD, Tel: 30 21 0213 3487, Fax: 30 21 0213 3487, Email: panos_hountis{at}hotmail.com, Evaggelismos General Hospital, Veikou 9-11, 11146 Athens, Greece.
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ABSTRACT
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Amiodarone is one of the commonly used anti-arrhythmic agents with well-recognized chronic pulmonary toxicity. We present our experience of a patient with a fatal outcome after coronary artery bypass grafting and a short course of amiodarone treatment with a low total cumulative dose for the treatment of postoperative atrial fibrillation. Necropsy revealed diffuse pulmonary damage due to acute amiodarone lung toxicity.
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INTRODUCTION
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Amiodarone, long used for various arrhythmias, has been associated with a long list of side effects. Chronic amiodarone pulmonary toxicity (CAPT) was first reported in 1980.1 However, development of this syndrome has predominately been described in patients receiving large doses of the drug over prolonged periods.2 Less well known is the potential of low dose amiodarone to cause acute lung damage which can be severe, or occasionally life threatening.3
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CASE REPORT
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A 74-year-old male was admitted to our department with three vessel ischemic heart disease, left main coronary artery stenosis of 90%, and an ejection fraction of 45%. Preoperative chest radiography and laboratory workup results were normal, and there were no other co-morbidities. Three vessel coronary artery bypass grafting (CABG) with a 45 minutes cross clamp ischemia time and 70 minutes on cardiopulmonary bypass was performed. The patient was extubated 12 hours after the operation with normal vital signs, a blood saturation of 95%, and normal arterial blood gases (pH 7.34; pO2 197; pCO2 34).
Six hours after extubation, the patient abruptly developed atrial fibrillation with a rapid ventricular response (150 beats·min–1). There was no hemodynamic clinical deterioration. Amiodarone therapy with intravenous loading (5 mg·kg–1) in 20 minutes was started. Subsequently, a continuous 24-hour intravenous infusion of amiodarone (750 mg/24 hours) was instituted. Although the ventricular response lowered to 95 beats·min–1 10 minutes after the infusion, the abnormal rhythm converted to sinus two hours later. The patient was febrile at 38°C and atrial fibrillation resumed.
A slight decrease in blood pressure (BP) to about 95/45 mm Hg was noted and inotropic support with dobutamine (20 mg·kg–1·min–1) was commenced. Progressively the patient complained of dyspnea with an oxygen saturation of 85% on oximetry requiring supplemental oxygen. Breathing sounds were decreased at the lung bases accompanied by bibasilar rales. A chest X-Ray showed bilateral alveolo-interstitial infiltrates. The patient was intubated again due to deterioration of arterial blood gases (pH 7.30; pO2 55; pCO2 45), base excess -6, severe dyspnea, and lowered mental status. Erythrocyte sedimentation rate was 156 and leukocyte count was elevated to 16.5 K/µL–1. Computed tomography (CT) scan revealed prominent bilateral densities mainly at the perihilar space radiating to the periphery with a ground glass appearance (Figure 1
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Figure 1. Bilateral density at the perihilar space radiating to the periphery, typical of acute respiratory distress syndrome.
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The patient was started on hydrocortisone without clinical improvement and continued to receive amiodarone because there was not a high possibility at that time that this may be the causative factor. Right heart catheterization was essentially normal with a cardiac output of 3.9 L·min–1·cm–2 and pulmonary capillary wedge pressure (PCWP) 10–14. Despite our management the patient was acidotic, hypoxic, and developed multisystem failure. The patient died after an episode of ventricular fibrillation. We referred the patient to our pathology department for postmortem necropsy.
Pathologic examination revealed diffusely deranged lung parenchyma with typical foamy cells, interstitial and intra-alveolar edema and hyaline membranes (PAS+) with diffuse dilatation of the airways and hyperplasia of the alveolar cells. Cytoplasmic swelling and varying amounts of hemorrhage, thrombosis, and fibrin deposition were seen in capillary endothelial cells. Sloughing of the alveolar lining cells and denudation of the epithelial basement membrane were also present. Areas of bronchiolitis obliterans-organising pneumonia (BOOP) were also found. We concluded that this patient suffered acute diffuse alveolar damage (DAD) with typical foamy cells due to acute amiodarone lung toxicity (Figure 2).
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Figure 2. Diffusely disordered lung parenchyma with widespread alveolar damage. (Diffuse alveolar damage: DAD)
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DISCUSSION
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Symptoms of acute lung toxicity developed without clear etiology in the early postoperative period, were attributed to cardiopulmonary bypass, and treated accordingly. The total cumulative dose of amiodarone the patient received was 1100 mg in 26 hours. This low cumulative dose led us to hypothesize that the occurrence and severity of acute amiodarone lung toxicity may not be dose related.
According to Daoud and colleagues4 who administered amiodarone 200 mg (orally, three times daily) for 7 days before cardiac surgery, and the Amiodarone Reduction in Coronary Heart (ARCH)5 trial in which 1 g of amiodarone IV was administered immediately postoperatively, this drug has proven to be an effective prophylactic agent in reducing the incidence of postoperative atrial fibrillation. Lungs of patients undergoing cardiac surgery are particularly susceptible to acute pulmonary toxicity (APT) and acute respiratory distress syndrome (ARDS) as a sequelae of cardiopulmonary bypass. Amiodarone impairs lipid metabolism resulting in damage to the pulmonary endothelium and generates toxic oxidants which contribute to the capillary leak syndrome observed in ARDS patients.6
Diagnosis is usually based on clinical and radiographic findings, the exclusion of differential alternatives, the demonstration of pulmonary function abnormalities compatible with APT, and typical foamy cells found in a lung biopsy specimen; but unfortunately in many cases it is a postmortem diagnosis.7 Due to the high mortality rate of postoperative ARDS in cardiac surgery we believe that the liberal preoperative administration of amiodarone needs further investigation and discussion.
The value of treatment with corticosteroids is unclear. In general, steroids are recommended when there is severe impairment of gas exchange. According to Lardinois et al,8 the management of patients with unexplained progressive respiratory insufficiency and bilateral parenchymal infiltrates after amiodarone administration must be with early, prolonged, and liberal use of steroids as the mortality rate among patients in whom ARDS develops is as high as 50%. However, other investigators disagree, and believe that steroid therapy should be used judiciously only after congestive heart failure and infectious etiologies have been ruled out.
The mortality rate is especially high in patients with underlying lung disease and compromised pulmonary function and in those with low ejection fractions; explaining the higher incidence after cardiac operations. This case indicates that amiodarone may provoke an acute onset of pulmonary toxicity even as early as hours after the induction of therapy, and with a low total cumulative dose.
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REFERENCES
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- Rotmensch HH, Liron M, Tupilsky M, Laniado S. Possible association of pneumonitis with amiodarone therapy. Am Heart J 1980; 100:412–3.[Medline]
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- Ott MC, Khoor A, Leventhal JP, Paterick TE, Burger CD. Pulmonary toxicity in patients receiving low-dose amiodarone. Chest 2003;123:646–51.[Medline]
- Daoud EG, Strickberger SA, Man KC, Goyal R, Deeb GM, Bolling SF, Pagani FD, Bitar C, Meissner MD, Morady F. Preoperative amiodarone as prophylaxis against atrial fibrillation after heart surgery. N Engl J Med. 1997 Dec 18;337(25):1785–91.[Abstract/Free Full Text]
- Guarnieri T, Nolan S, Gottlieb SO, Dudek A, Lowry DR. Intravenous amiodarone for the prevention of atrial fibrillation after open heart surgery: the Amiodarone Reduction in Coronary Heart (ARCH) trial. J Am Coll Cardiol 1999;34:343–7.[Abstract/Free Full Text]
- Ashrafian H, Davey P. Is amiodarone an underrecognized cause of acute respiratory failure in the ICU? Chest 2001;120:275–82.[Medline]
- Dean PJ, Groshart KD, Porterfield JG, Iansmith DH, Golden EB Jr. Amiodarone-associated pulmonary toxicity. A clinical and pathologic study of eleven cases. Am J Clin Pathol 1987;87:7–13.[Medline]
- Lardinois D, Handschin A, Weder W. Acute amiodarone-induced pulmonary toxicity after lung operation. Ann Thorac Surg 2002;73:2033–4.[Free Full Text]
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ABSTRACT
INTRODUCTION
