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Effects of Dexmedetomidine on Myocardial Repolarization in Children Undergoing General Anesthesia: A Randomized Controlled Trial

Görges, Matthias PhD*,†; Sherwin, Elizabeth D. MD; Poznikoff, Andrew K. BSc*,§; West, Nicholas C. MSc*; Brodie, Sonia M. MSc*; Whyte, Simon D. MBBS, FRCA, FRCPC*,†,§

doi: 10.1213/ANE.0000000000004135
Pediatric Anesthesiology: Original Clinical Research Report
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BACKGROUND: Dexmedetomidine is a highly selective α2-adrenergic agonist, which is increasingly used in pediatric anesthesia and intensive care. Potential adverse effects that have not been rigorously evaluated in children include its effects on myocardial repolarization, which is important given that the drug is listed as a possible risk factor for torsades de pointes. We investigated the effect of 3 different doses of dexmedetomidine on myocardial repolarization and transmural dispersion in children undergoing elective surgery with total IV anesthesia.

METHODS: Sixty-four American Society of Anesthesiologists I–II children 3–10 years of age were randomized to receive dexmedetomidine 0.25 µg/kg, 0.5 µg/kg, 0.75 µg/kg, or 0 µg/kg (control), as a bolus administered over 60 seconds, after induction of anesthesia. Pre- and postintervention 12-lead electrocardiograms were recorded. The interval between the peak and the end of the electrocardiogram T wave (Tp-e; transmural dispersion) and heart rate–corrected QT intervals (myocardial repolarization) were measured by a pediatric electrophysiologist blinded to group allocation. Data were analyzed using an analysis of covariance regression model. The study was powered to detect a 25-millisecond difference in Tp-e.

RESULTS: Forty-eight children completed the study, with data analyzed from 12 participants per group. There were no instances of dysrhythmias. Tp-e values were unaffected by dexmedetomidine administration at any of the studied doses (F = 0.09; P = .96). Mean (99% CI) within-group differences were all <2 milliseconds (−5 to 8). Postintervention, corrected QT interval increased in the control group, but decreased in some dexmedetomidine groups (F = 7.23; P < .001), specifically the dexmedetomidine 0.5 and 0.75 µg/kg doses. Within groups, the mean (99% CI) differences between pre- and postintervention corrected QT interval were 12.4 milliseconds (−5.8 to 30.6) in the control group, −9.0 milliseconds (−24.9 to 6.9) for dexmedetomidine 0.25 µg/kg, −18.6 milliseconds (−33.7 to −3.5) for dexmedetomidine 0.5 µg/kg, and −14.1 milliseconds (−27.4 to −0.8) for dexmedetomidine 0.75 µg/kg.

CONCLUSIONS: Of the bolus doses of dexmedetomidine studied, none had an effect on Tp-e and the dexmedetomidine 0.5 and 0.75 µg/kg doses shortened corrected QT intervals when measured at 1 minute after dexmedetomidine bolus injection during total IV anesthesia. There is no evidence for an increased risk of torsades de pointes in this context.

From the *Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada

Research Institute, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada

Division of Cardiology, Children’s National Heart Institute, Washington, DC

§Department of Pediatric Anesthesia, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada.

Published ahead of print 15 February 2019.

Accepted for publication February 15, 2019.

Funding: Supported in part by a 2015 Evidence to Innovation Seed Grant from the British Columbia Children’s Hospital Research Institute.

The authors declare no conflicts of interest.

Data were previously presented in abstract form at the 2018 International Anesthesia Research Society Annual Meeting and International Science Symposium, Chicago, IL, April 28–May 1, 2018.

Trial registration: clinicaltrials.gov (NCT02353169).

Reprints will not be available from the authors.

Address correspondence to Simon D. Whyte, MBBS, FRCA, FRCPC, Department of Anesthesia, British Columbia Children’s Hospital Research Institute, Rm V3-355, 950 W 28th Ave, Vancouver, BC V5Z 4H4, Canada. Address e-mail to swhyte@cw.bc.ca.

Copyright © 2019 International Anesthesia Research Society
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