Etchegoyen Cecilia Villa, Keller Guillermo Alberto, Mrad Sebastian, Cheng Sixuan, Di Girolamo Guillermo
University of Buenos Aires, Faculty of Medicine, Drug Safety and Surveillance Center, Laboratory of Cardiovascular Safety of Drugs, Buenos Aires, Argentina.
University of Buenos Aires, Faculty of Medicine, Institute of Cardiological Research "Prof. Dr. Alberto C. Taquini", Buenos Aires, Argentina.
Curr Clin Pharmacol. 2017;12(4):210-222. doi: 10.2174/1574884713666180223123947.
The most common acquired cause of Long QT syndrome (LQTS) is drug induced QT interval prolongation. It is an electrophysiological entity, which is characterized by an extended duration of the ventricular repolarization. Reflected as a prolonged QT interval in a surface ECG, this syndrome increases the risk for polymorphic ventricular tachycardia (Torsade de Pointes) and sudden death.
Bibliographic databases as MEDLINE and EMBASE, reports and drug alerts from several regulatory agencies (FDA, EMEA, ANMAT) and drug safety guides (ICH S7B, ICH E14) were consulted to prepare this article. The keywords used were: polymorphic ventricular tachycardia, adverse drug events, prolonged QT, arrhythmias, intensive care unit and Torsade de Pointes. Such research involved materials produced up to December 2017.
Because of their mechanism of action, antiarrhythmic drugs such as amiodarone, sotalol, quinidine, procainamide, verapamil and diltiazem are associated to the prolongation of the QTc interval. For this reason, they require constant monitoring when administered. Other noncardiovascular drugs that are widely used in the Intensive Care Unit (ICU), such as ondansetron, macrolide and fluoroquinolone antibiotics, typical and atypical antipsychotics agents such as haloperidol, thioridazine, and sertindole are also frequently associated with the prolongation of the QTc interval. As a consequence, critical patients should be closely followed and evaluated.
ICU patients are particularly prone to experience a QTc interval prolongation mainly for two reasons. In the first place, they are exposed to certain drugs that can prolong the repolarization phase, either by their mechanism of action or through the interaction with other drugs. In the second place, the risk factors for TdP are prevalent clinical conditions among critically ill patients. As a consequence, the attending physician is expected to perform preventive monitoring and ECG checks to control the QTc interval.
长QT综合征(LQTS)最常见的后天性病因是药物诱发的QT间期延长。它是一种电生理实体,其特征是心室复极化持续时间延长。在体表心电图上表现为QT间期延长,该综合征增加了多形性室性心动过速(尖端扭转型室速)和猝死的风险。
查阅了MEDLINE和EMBASE等文献数据库、几个监管机构(美国食品药品监督管理局、欧洲药品管理局、阿根廷药品、食品和医疗技术管理局)的报告及药品警示以及药品安全指南(国际人用药品注册技术协调会S7B、国际人用药品注册技术协调会E14)来撰写本文。使用的关键词有:多形性室性心动过速、药物不良事件、QT延长、心律失常、重症监护病房和尖端扭转型室速。此类研究涉及截至2017年12月的资料。
由于其作用机制,胺碘酮、索他洛尔、奎尼丁、普鲁卡因胺、维拉帕米和地尔硫䓬等抗心律失常药物与QTc间期延长有关。因此,给药时需要持续监测。重症监护病房(ICU)中广泛使用的其他非心血管药物,如昂丹司琼、大环内酯类和氟喹诺酮类抗生素,以及典型和非典型抗精神病药物如氟哌啶醇、硫利达嗪和舍吲哚,也经常与QTc间期延长有关。因此,对重症患者应密切随访和评估。
ICU患者特别容易出现QTc间期延长,主要有两个原因。首先,他们接触到某些可通过其作用机制或与其他药物相互作用而延长复极期的药物。其次,尖端扭转型室速的危险因素在重症患者中是普遍存在的临床情况。因此,主治医师应进行预防性监测和心电图检查以控制QTc间期。