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The effect of carbetocin dose on transmural dispersion of myocardial repolarization in healthy parturients scheduled for elective cesarean delivery under spinal anesthesia – A prospective, randomized clinical trial
Abstract Number: GM-01
Abstract Type: Original Research
Introduction: QT prolongation is associated with torsades des pointes but remains a poor predictor of drug torsadogenicity. Increased transmural dispersion of repolarization, measured as the time interval between the peak and end of the T wave (Tp-e), is a more reliable predictor. Carbetocin is recommended as an uterotonic in patients undergoing cesarean delivery (CD), but its effect on Tp-e is unknown. We evaluated the effect of carbetocin dose on Tp-e and Bazett-corrected QT (QTc) intervals during elective CD under spinal anesthesia. We hypothesized that carbetocin would dose-dependently increase Tp-e intervals.
Methods: Upon patient consent, 40 healthy patients undergoing elective CD with a standardized spinal anesthetic and phenylephrine infusion were randomized to receive an IV bolus of carbetocin 50 mcg (C50) or 100 mcg (C100) via an infusion pump over 1 min. 12-lead ECGs were obtained at baseline, 5 min post-spinal, then 5 and 10 min post-carbetocin. A cardiologist blinded to group and timing of ECGs measured QTc and Tp-e intervals using Emori’s criteria. Primary outcome was the change in Tp-e at 5 min post-carbetocin between and within groups, analyzed by mixed-effects linear regression. Secondary outcomes included occurrence of arrhythmias, changes in QTc at 5 min and 10 min post-carbetocin, changes in both QTc and Tp-e post-spinal compared to baseline between and within groups. P-values were adjusted for multiple comparisons.
Results: Between groups, at 5 min post-carbetocin, Tp-e in C100 was 4.0 msec longer compared to C50 (95%CI=0.3-7.8, p=0.03). Within groups, at 5 min post-carbetocin C50 did not significantly increase Tp-e compared to baseline (2.4 msec; p=0.25) but C100 did (4.9 msec; 95%CI=1.8-8.1; p=0.008). QTc increased significantly within C50 and C100 groups at 5 and 10 min post-carbetocin (all p<0.001), with no between-group differences. There were no arrhythmias. (see Fig)
Discussion: Tp-e was unaffected by carbetocin 50 mcg IV given post-CD in healthy parturients under spinal anesthesia, but slightly prolonged by 100 mcg. The increase in QTc post-carbetocin was significant, with no apparent dose-dependent effect. Although the minimal Tp-e prolongation at the higher dose is unlikely to be clinically significant, these findings suggest a lower carbetocin dose may be preferred in parturients with reduced repolarization reserve.
1.Hume-Smith H, A&A 2008
2.Bruyere M, IJOA. 2014
3.Emori T, J Cardiovasc Electrophysiol. 2001