Current concepts in the mechanisms and management of drug-induced QT prolongation and torsade de pointes.

Drug-induced long QT syndrome is characterized by a prolonged corrected QT interval (QTc) and increased risk of a polymorphic ventricular tachycardia known as torsade de pointes (TdP). We review mechanisms, predispositions, culprit agents, and management of this potentially fatal phenomenon. Virtually all drugs that prolong QTc block the rapid component of the delayed rectifier current (I(kr)). Some drugs prolong QTc in a dose-dependent manner, others do so at any dose. Most patients that develop drug-induced TdP have underlying risk factors. Female sex is the most common. Implicated drugs include class 1A and III antiarrhythmics, macrolide antibiotics, pentamidine, antimalarials, antipsychotics, arsenic trioxide, and methadone. Treatment for TdP includes immediate defibrillation for hemodynamic instability and intravenous magnesium sulfate. Potassium levels should be maintained in the high normal range, and all QT prolonging agents must be promptly discontinued.

Amiodarone prophylaxis reduces major cardiovascular morbidity and length of stay after cardiac surgery: a meta-analysis.

BACKGROUND: Although evidence supports the prophylactic use of beta-blockade in cardiac surgery, postoperative atrial fibrillation or flutter occurs in 40% to 60% of patients. Trials that assessed whether amiodarone prophylaxis decreases the incidence of postoperative atrial tachyarrhythmias have had mixed results and were not specifically powered to detect changes in cardiovascular morbidity, length of stay, or mortality. PURPOSE: To see whether prophylactic administration of amiodarone decreases the incidence of major cardiovascular events, length of stay, and mortality after cardiac surgery. DATA SOURCES: English-language and non-English-language publications listed in the MEDLINE, EMBASE, and CINAHL databases and the Cochrane Central Register of Controlled Trials, and bibliographies of published reviews. Sources were searched from the earliest possible dates through February 2005. STUDY SELECTION: Double-blind, randomized studies comparing amiodarone with placebo that reported the incidence of supraventricular arrhythmia, atrial fibrillation, or atrial flutter as the primary end point. DATA EXTRACTION: Two investigators independently collected all data. Discrepancies were resolved by consensus. DATA SYNTHESIS: After DerSimonian-Laird random-effects models were used to combine data from 10 trials involving 1744 patients, amiodarone therapy was found to decrease the incidence of atrial fibrillation or flutter (relative risk, 0.64 [95% CI, 0.55 to 0.75]), ventricular tachycardia and fibrillation (relative risk, 0.42 [CI, 0.28 to 0.63]), stroke (relative risk, 0.39 [CI, 0.21 to 0.76]), and length of stay (weighted mean difference, -0.63 day [CI, -1.03 to -0.23 days]). All studies reported adverse events, but none indicated how these events were assessed. Three studies found significantly more adverse events with amiodarone therapy, including nausea permitting continuation of therapy, bradycardia of unclear clinical significance, and increased intensive care monitoring and support. LIMITATIONS: Not all studies used beta-blockade, and regimens were not uniform among trials. Few trials met the stringent inclusion criteria, some did not report each type of cardiovascular event, and none reported completeness of follow-up. CONCLUSIONS: Amiodarone prophylaxis decreases the occurrence of atrial fibrillation, ventricular tachyarrhythmias, and stroke and length of stay after cardiac surgery. To further evaluate the potential benefits of concomitant prophylaxis with beta-blockers and amiodarone, a multicenter, randomized, double-blind trial with cardiovascular outcomes that compares amiodarone with placebo in patients already receiving beta-blocker prophylaxis is needed.