Acute liver failure induced by intravenous amiodarone in the cardiac care unit: retrospective study of 3 years

Introduction

Amiodarone is the antiarrhythmic drug of choice in treatment of patients suffering from acute tachyarrhythmias and haemodynamic instability due to impaired cardiac function. The intravenous form of amiodarone hydrochloride (IvAm) has individual antiarrhythmic, rate-controlling efficacy, and the dosage is empirical. The main adverse effects are hypotension, severe bradycardia, asystole, acute heart failure, and impaired liver function. Acute liver failure (ALF) is a known but rare complication of IvAm that may be reversible by eliminating the infusion in most cases. The few papers in the literature suppose ALF may be caused by polysorbate 80, the vehicle of IvAm. Oral administration does not to have such an adverse effect, therefore IvAm can be changed to oral form in any cases.

Methods

Our aim was to investigate retrospectively the incidence of ALF and relation of IvAm and ALF in cardiac patients. The history, treatment sheets and laboratory parameters of 11,722 patients treated in the Heart Center between 2005 and 2007 were analyzed. Patients were considered severe ALF patients if transaminase levels exceeded 80 × upper limit of normal (ULN) during their stay in our clinic. The cutoff point was determined to differentiate ALF patients from heart failure and myocardial infarct patients with elevated transaminase levels.

Results

According to the enzyme levels, 55 patients suffered from severe ALF during the 3 years; 26 of them had IvAm treatment. On the basis of treatment sheets, start and elimination of IvAm treatment, status of acute myocardial infarct and heart failure and transaminase kinetics, eight patients had ALF induced by IvAm. Indication for amiodarone was atrial fibrillation (n = 6) and ventricular tachycardia. Average multipliers of ULN were 379 ± 190 at aspartate aminotransferase, 191 ± 87 at alanine aminotransferase, 57 ± 22 at lactate dehydrogenase. The time from start of IvAm to detection of ALF was 17 ± 4.6 hours. One-quarter of these patients died in ALF. Liver enzymes decreased to 10 × ULN during 2.5 ± 0.6 days.

Conclusion

ALF is a rare but potentially life-threatening adverse effect of IvAm. Authors suggest monitoring liver enzymes from the start of IvAm treatment. Rapid elevation in liver enzyme levels indicates a hepatotoxic effect of IvAm. In these cases the immediate cessation of IvAm administration and start of intensive care is lifesaving.