The effect of propofol dose on myocardial repolarization in children

Abstract

Introduction: Acquired QT interval prolongation on the ECG is commonly drug-induced, and is traditionally associated with torsades de pointes (TdP). A better predictor of TdP is the time interval between the peak and the end of the T wave (Tp-e)(1). Sevoflurane prolongs the corrected QT interval (QTc), although the Tp-e remains unaffected(2). In contrast, target controlled infusion of propofol at 3 μg/mL has no effect on QTc or Tp-e. This plasma concentration of propofol is at the extreme lower end of the range for surgical anesthesia. The purpose of this randomised double-blind clinical study was to investigate the dose-response relationship between propofol, QTc and Tp-e in a range of doses clinically relevant for surgical anesthesia. Methods: Written ethics committee approval and consent was obtained. 60 healthy unpremedicated children, aged 3-10 years, were recruited. Subjects were randomised to receive target controlled infusions of propofol, to achieve one of three plasma concentrations: 3μg/mL, 4.5μg/mL and 6μg/mL. A pre-operative 12 lead ECG was performed and repeated 5 minutes post induction. Two investigators, blinded to the group allocation and to the timing of the ECG traces, independently measured QTc and Tp-e within and between each group. Paired t-tests were used to compare QTc and Tp-e within groups. One way analysis of variance was used for inter-group analysis. The primary outcome measure was a change of >25msec in Tp-e both within and between groups.