Volatile Anesthetics and the Long QT Syndrome

Abstract

*University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. stefan.rasche@uniklinikum-dresden.deWith much interest we read the article by Susan J. Kies et al. regarding patients with congenital long QT syndrome (LQTS). We congratulate the authors on their excellent review but would like to discuss several aspects. As stated in the introduction, patients with LQTS often show a “delayed cellular repolarization and heterogeneity in dispersion of repolarization, which … can lead to early after-depolarization, further dispersion of repolarization, and the formation of reentry circuits.”It becomes increasingly apparent that the QT interval prolongation per se is not the crucial pathology in LQTS. The delayed cellular repolarization in LQTS represents either impaired rapid or slow delayed rectifier potassium currents (iKr or iKs) or inappropriately inactivated sodium currents (iNa). The main arrhythmogenic substrate resulting from these altered ion currents is an increase in transmural repolarization heterogeneity. This heterogeneity favors the development of torsade de pointes, which is triggered by early after-depolarizations. More than 300 mutations in six genes encoding cardiac ion channel subunits and ankyrin B have been identified in patients with LQTS. According to the affected ion channel subunit, LQTS is classified into six subtypes with partially different clinical courses and triggers of torsade de pointes. Hence, the clinical and electrophysiologic presentations of the syndrome are considerably heterogeneous, and the effects of different drugs may be unpredictable.The QT interval obtained by a 12-lead electrocardiogram is only a rough measure of the repolarization time. Diagnosis based solely on summation vectors projected to the body surface is therefore neither sensitive nor specific. Accordingly, studies that only focus on drug effects on the QT interval may produce premature conclusions regarding potential safety or risk of these drugs in LQTS. This explains the contradicting results of numerous investigations, which report different effects of drugs on QT interval. Kies et al. recommend isoflurane as volatile anesthetic of choice in LQTS patients. In our opinion, to date, such recommendation cannot be supported. The reported effects of volatile anesthetics on QT interval are inconsistent or even conflicting. Only few studies have focused on QT heterogeneity or ion channel physiology, and it seems that all volatile anesthetics—including isoflurane—interact directly with cardiac delayed rectifier potassium channels.8,9,10,11 We therefore propose to avoid this class of anesthetics and would prefer propofol as the anesthetic of choice until more information is available from pharmacologic studies that focus on ion channel physiology and transmural heterogeneity of repolarization. These studies should ideally differentiate between LQTS subtypes.*University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. stefan.rasche@uniklinikum-dresden.de