Hepatotoxicity during rapid intravenous loading with amiodarone: Description of three cases and review of the literature*

Objective:Atrial fibrillation is the most common arrhythmia after cardiac surgery. Amiodarone can effectively prevent and control postoperative atrial and ventricular fibrillation. Acute hepatic damage after intravenous amiodarone, which can be fatal, is not well recognized. We describe three cases of acute hepatocellular injury after intravenous amiodarone administration in critically ill patients. Another 25 published cases and six cases reported to the Swiss Pharmacovigilance Center (Swissmedic) are discussed. Design:This study consisted of a series of three case reports and review of the literature. Setting:This study was conducted at an operative critical care unit at the University Hospital Basel, Switzerland. Patients:Three hemodynamically compromised patients after open heart surgery developed significant increases of transaminases (up to more than 100-fold of the upper limit of normal) shortly after the introduction of intravenous amiodarone. Interventions and Measurement:Cessation of intravenous amiodarone and of other potentially hepatotoxic drugs. Results:Liver parameters significantly improved or returned to normal in all three patients, even after start of oral amiodarone in two patients. Conclusions:Amiodarone is a highly effective antiarrhythmic agent for the treatment and prevention of atrial and ventricular arrhythmias. Acute liver damage after intravenous amiodarone, possibly induced by the solubilizer polysorbate 80, is rare but potentially harmful. Amiodarone loading should therefore be adapted to the necessity of an immediate effect of the drug, and liver function should be monitored closely in critically ill patients. Oral maintenance therapy with amiodarone is possible, even in patients who developed liver disease during intravenous loading.