Incidence of and Predicting Factors for Torsades de Pointes during Intravenous Administration of Amiodarone

Abstract

Objective: There is considerable knowledge of the incidence of torsades de pointes (TdP) during the administration of amiodarone The aim of our study was to determine the incidence of TdP during the loading phase of intravenous administration of amiodarone, intended to reverse paroxysmal atrial fibrillation (PAF) to sinus rhythm (SR), and to test the hypothesis that their prevalence is greater among women than men, as reported earlier. We also sought to determine factors predisposing to the occurrence of TpD, such as atrium size and hyperglycemia. Methods: We evaluated 189 patients (M = 107, F = 82, mean age = 56 ± 19 years), who were admitted for PAF, and for whom amiodarone was selected as the first-choice drug for PAF reversion. During the first 24 h of the loading phase (300 mg rapid i.v. administration within 20 min and 1,500 mg i.v. for 24 h) we recorded all ventricular arrhythmias. All patients were on anticoagulant treatment and all of them were evaluated for corrected QT (QTc), as well as additional risk factors (atrial size, serum glucose, hypopotassemia, hypomagnesemia, severe bradycardia). Patients with heart failure, hypertrophic obstructive cardiomyopathy, a history of coronary artery disease or ventricular tachycardia, as well as those treated with drugs prolonging the QT interval, were excluded from the study. Results: 108 patients (57.1%) experienced successful conversion of PAF into SR on amiodarone. Five patients (2.6%), all female, mean age 53.0 ± 1.2 years, developed TpD. All episodes occurred at the end of the loading phase (21–24 h) of amiodarone administration. None of them had hypopotassemia, hypomagnesemia, or bradycardia (HR <55 bpm). Two of the TpD patients had elevated glucose levels, and all of them had prolonged QTc immediately prior to the TpD. Conclusion: We confirm that women are at increased risk of developing TpD during the administration of amiodarone. TpD develop towards the end of the intravenous loading phase; the electrocardiographic changes should be closely monitored towards the end of the loading phase. The presence of diabetes mellitus or temporal hyperglycemia and prolonged QTc seems to be predicting factors for TpD during i.v. amiodarone administration.

Amiodarone: The Last and/or Best Hope for Pharmacological Control of Cardiac Arrhythmias?

“…The kinetics of the onset of drug effects are consistent with the finding in this study [1] of TdP occurring at the end of loading.…”

“…The main problem is that the risk-benefit ratio of pharmacological control may be unfavorable particularly when the rhythm being treated is not life threatening. Psirropoulos et al [1] highlight one of the most important risks of amiodarone, the potential for druginduced proarrhythmia, the result of prolongation of ventricular repolarization. This study finds the incidence to be 2.6% (5 patients of a total of 186) in a cohort with atrial fibrillation without heart failure or hypertrophic cardiomyopathy.…”

Incidence of drug-induced torsades de pointes with intravenous amiodarone

“… 9 In a series patients treated with IV amiodarone for atrial arrhythmias, the incidence of TdP has been reported to be 2.6%. 10 In an epidemiological study of drug-induced LQTS from Germany, amiodarone was the most common cause in 10 out of 35 cases. The drug was administered intravenously in half of these patients making.…”

“…12 Women appear to be at increased risk of drug-induced TdP in many of the studies. 5 , 10 , 11 Other risk factors include hypokalemia, 11 pretreatment with digoxin, 13 triple therapy with beta-blockers, digoxin, and amiodarone, 14 and left ventricular dysfunction. 15 The hallmark of drug-induced TdP with amiodarone is, prolongation of QTc in patients with normal QTc before initiation, pause dependent onset, polymorphic VT degenerating to VF, and normalization of QTc 48–72 h after drug withdrawal.…”

Torsade de Pointes in a Patient with Acute Prolonged QT Syndrome and Poorly Controlled Diabetes during Sevoflurane Anaesthesia

“…In critically ill patients, BSL is an independent predictor of prolonged QTc interval 6 . Diabetes mellitus and temporal hyperglycaemia have also been identified as predisposing factors for the development of TdP during intravenous amiodarone therapy 7 .…”