Amiodarone-Related Acute Respiratory Distress Syndrome following Sudden Withdrawal of Steroids

Charles, Pierre‐Emmanuel; Doise, Jean; Quenot, Jean‐Pierre; Müller, G.; Aube, Hervé; Baudouin, Nicolas; Piard, F; Besancenot, J.-F.; Blettery, B

doi:10.1159/000088010

Cited by 14 publications

(5 citation statements)

References 11 publications

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“…It was initially believed that a low dose of AD was relatively safe, but more recent case reports have revealed a high risk of pulmonary complications, especially confluent lung fibrosis, even with low dosage treatment of patients (200 mg per day). Acute respiratory distress syndrome and pneumonitis are also well‐documented side effects of AD . Hence, according to the recent guideline for the management of patients with atrial fibrillation, AD is prescribed to treat atrial fibrillation in the absence of pre‐excitation only when other agents are unsuccessful .…”

Section: Introductionmentioning

confidence: 99%

Regulation of macroautophagy in amiodarone‐induced pulmonary fibrosis

Mahavadi

Knudsen

Venkatesan

et al. 2015

The Journal of Pathology CR

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Amiodarone (AD) is an iodinated benzofuran derivative, especially known for its antiarrhythmic properties. It exerts serious side‐effects even in patients receiving low doses. AD is well‐known to induce apoptosis of type II alveolar epithelial cells (AECII), a mechanism that has been suggested to play an important role in AD‐induced lung fibrosis. The precise molecular mechanisms underlying this disease are, however, still unclear. Because of its amphiphilic nature, AD becomes enriched in the lysosomal compartments, affecting the general functions of these organelles. Hence, in this study, we aimed to assess the role of autophagy, a lysosome‐dependent homeostasis mechanism, in driving AECII apoptosis in response to AD. In vitro, AD‐treated MLE12 and primary AECII cells showed increased proSP‐C and LC3B positive vacuolar structures and underwent LC3B‐dependent apoptosis. In addition, AD‐induced autophagosome‐lysosome fusion and increased autophagy flux were observed. In vivo, in C57BL/6 mice, LC3B was localised at the limiting membrane of lamellar bodies, which were closely connected to the autophagosomal structures in AECIIs. Our data suggest that AD causes activation of macroautophagy in AECIIs and extensive autophagy‐dependent apoptosis of alveolar epithelial cells. Targeting the autophagy pathway may therefore represent an attractive treatment modality in AD‐induced lung fibrosis.

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Section: Introductionmentioning

confidence: 99%

Regulation of macroautophagy in amiodarone‐induced pulmonary fibrosis

Mahavadi

Knudsen

Venkatesan

et al. 2015

The Journal of Pathology CR

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“…Low dose of AD (200 mg/day) was believed to be relatively safe, but increasing evidence suggests the risk of pulmonary complications, especially lung fibrosis, even in low dosage treatment group of patients. Apart from pulmonary fibrosis, pneumonitis and acute respiratory distress syndrome (ARDS) are also well documented as potential side effects of AD (Chang et al, 2007;Charles et al, 2006). According to a statistical analysis published in 1999 (Connolly, 1999), AD accounted for 24.1% of the total antiarrhythmic prescriptions in 1998.…”

mentioning

confidence: 99%

Altered Surfactant Homeostasis and Alveolar Epithelial Cell Stress in Amiodarone-Induced Lung Fibrosis

Mahavadi

Henneke

Ruppert

et al. 2014

Toxicological Sciences

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Amiodarone (AD) is a highly efficient antiarrhythmic drug with potentially serious side effects. Severe pulmonary toxicity is reported in patients receiving AD even at low doses and may cause interstitial pneumonia as well as lung fibrosis. Apoptosis of alveolar epithelial type II cells (AECII) has been suggested to play an important role in this disease. In the current study, we aimed to establish a murine model of AD-induced lung fibrosis and analyze surfactant homeostasis, lysosomal, and endoplasmic reticulum (ER) stress in this model. AD/vehicle was instilled intratracheally into C57BL/6 mice, which were sacrificed on days 7, 14, 21, and 28. Extent of lung fibrosis development was assessed by trichrome staining and hydroxyproline measurement. Cytotoxicity was assessed by lactate dehydrogenase assay. Phospholipids (PLs) were analyzed by mass spectrometry. Surfactant proteins (SP) and markers for apoptosis, lysosomal, and ER stress were studied by Western blotting and immunohistochemistry. AECII morphology was evaluated by electron microscopy. Extensive lung fibrosis and AECII hyperplasia were observed in AD-treated mice already at day 7. Surfactant PL and SP accumulated in AECII over time. In parallel, induction of apoptosis, lysosomal, and ER stress was encountered in AECII of mice lungs and in MLE12 cells treated with AD. In vitro, siRNA-mediated knockdown of cathepsin D did not alter the AD-induced apoptotic response. Our data suggest that mice exposed to intratracheal AD develop severe pulmonary fibrosis, exhibit extensive surfactant alterations and cellular stress, but AD-induced AECII apoptosis is not mediated primarily via cathepsin D.

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“…Other important side effects include corneal microdeposits, hepatic dysfunction (1-2% in intravenous use) [76,77], pulmonary fibrosis (in 5-10%), slowly progressive interstitial pneumonia with bilateral diffuse infiltrates [78,79], skin discoloration and neuropathies [71,72].…”

Section: Amiodaronementioning

confidence: 99%

Management of arrhythmia in sepsis and septic shock

Borggrefe¹,

Matoušek²,

Malý³

et al. 2017

Anaesthesiol Intensive Ther

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The occurrence of supraventricular arrhythmias is associated with an unfavourable prognosis in septic shock. Available trials are difficult to apply in sepsis and septic shock patients due to included cohorts, control groups and because "one size does not fit all". The priorities in the critically ill are maintenance of the sinus rhythm and diastolic ventricular filling. The rate control modality should be reserved for chronic AF and in situations when the sinus rhythm is difficult to maintain due to extreme stress conditions resulting from a high dosage of vasoactive agents. Electric cardioversion is indicated in unstable patients with an absence of contraindications and is more feasible in combination with an antiarrhythmic agent. Besides amiodarone being preferred for its lower cardiodepressant side effect compared to other agents, drugs with a different degree of betablocking activity are very useful in supraventricular arrhythmias and septic shock, providing echocardiography is routinely used to support their indications within the current summary of product characteristics. A typical patient benefiting from propafenone is without significant structural heart disease, i.e. typically with normal to moderately reduced left ventricular systolic function. Future research should be channelled towards echocardiography-guided prospective controlled trials on antiarrhythmic therapy which may clarify the issue of rhythm versus rate control, the effects of various antiarrhythmic drugs, and a place for electric cardioversion in critically ill patients in septic shock.

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Amiodarone-Related Acute Respiratory Distress Syndrome following Sudden Withdrawal of Steroids

Cited by 14 publications

References 11 publications

Regulation of macroautophagy in amiodarone‐induced pulmonary fibrosis

Regulation of macroautophagy in amiodarone‐induced pulmonary fibrosis

Altered Surfactant Homeostasis and Alveolar Epithelial Cell Stress in Amiodarone-Induced Lung Fibrosis

Management of arrhythmia in sepsis and septic shock

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