A Comparison of the Effect on Dispersion of Repolarization of Age-Adjusted MAC Values of Sevoflurane in Children

Abstract

QT interval prolongation is associated with torsades des pointes (TdP), but is a poor predictor of drug torsadogenicity. Susceptibility to TdP arises from increased transmural dispersion of repolarization (TDR) across the myocardial wall, rather than QT interval prolongation per se. TDR can be measured on the electrocardiogram as the time interval between the peak and end of the T-wave (Tp-e). Thus Tp-e is a readily measured assay of drug torsadogenicity. Several anesthetic drugs prolong the QT interval, but their effect on TDR is largely unknown. We investigated the effects of sevoflurane on corrected QT (QTc) and Tp-e intervals in 54 unpremedicated ASA I-II children, aged 3-10 yr, who were randomized to receive sevoflurane 1, 1.25, or 1.5 MAC, age-adjusted. Twelve-lead electrocardiograms were recorded before and after sevoflurane exposure. QTc and Tp-e were compared within and among groups using 2-way analysis of variance. Change in Tp-e after sevoflurane exposure was the primary outcome measure. Sevoflurane significantly prolonged preoperative QTc at all doses (P < 0.005), with no dose-response relationship, but had no effect on preoperative Tp-e. Sevoflurane markedly prolongs the QTc in healthy children, but does not increase dispersion of repolarization as measured by the Tp-e interval, indicating low or no torsadogenicity, and making it unlikely to increase predisposition to TdP.