The effect of propofol concentration on dispersion of myocardial repolarization in children.
BACKGROUND
QT interval prolongation on the electrocardiogram (ECG) may be drug-induced and is traditionally associated with torsades des pointes. A better predictor of torsades des pointes is the time interval between the peak and the end of the T-wave (Tp-e). Older studies of propofol's effect on the corrected interval (QTc) are conflicting and confounded by polypharmacy. It was recently shown that target-controlled infusion of propofol at 3 microg/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. In this randomized, double-blind, clinical study, we investigated the dose-response relationship between propofol, QTc, and Tp-e in a range of doses clinically relevant for surgical anesthesia.


METHODS
Sixty healthy unpremedicated children, aged 3-10 yr, were recruited. Subjects were randomized to receive target-controlled infusions of propofol, to achieve 1 of 3 plasma concentrations: 3, 4.5, and 6 microg/mL. A preoperative 12 lead ECG was performed and repeated 5 min after induction. Two investigators, blinded to 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 intergroup analysis. The primary outcome measure was a change of >25 ms in Tp-e both within and between groups.


RESULTS
ECG recordings were obtained in 51 children. There were no demographic or ECG differences at baseline, at which time QTc and Tp-e values were within normal limits. There were no differences in QTc or Tp-e after induction within or between the three different groups.


CONCLUSIONS
Propofol has no effect on myocardial repolarization in healthy children at clinically relevant doses. This suggests that propofol would be a rational choice for children with a preexisting repolarization abnormality.
Hume-Smith
Helen V
HV
Department of Pediatric Anesthesia, British Columbia Children's Hospital, 4480 Oak St., Vancouver, BC, V6H 3V4, Canada.
Sanatani
Shubhayan
S
Lim
Joanne
J
Chau
Anthony
A
Whyte
Simon D
SD
D000758:Anesthesia / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D004562:Electrocardiography / Q000379:methods*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D006801:Humans; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D015742:Propofol / Q000627:therapeutic use*; D016171:Torsades de Pointes / Q000378:metabolism
D015742:Propofol