The Effects of Dexmedetomidine on the Heart Beat During Elective Surgery in Children
Condition: Myocardial Repolarization; Healthy
Study type: Interventional
Phase: Phase 4

Summary: 
      Dexmedetomidine is a sedative drug that is commonly used to improve calmness and reduce pain
      in children waking up after surgery. Some of the side effects of dexmedetomidine, such as a
      potential change in how the heart muscles contract and changes in blood sugar and potassium
      levels, are poorly understood. The current study aims to examine these changes directly in
      healthy children undergoing elective surgery by measuring the heart beats (with an
      electrocardiogram) and blood sugar and potassium at specific times before and after
      dexmedetomidine is given. The investigators aim to establish a better understanding of this
      drug's safety profile.
    

Detailed description: 
      Purpose:

      This study is being conducted to evaluate the effect of three different doses of
      dexmedetomidine (Precedex® , Hospira Healthcare) on myocardial repolarization, and blood
      glucose and potassium levels in children undergoing elective surgery.

      Hypotheses:

      The investigators hypothesize that administering a dexmedetomidine bolus will have some
      effect on myocardial repolarization, blood glucose, and potassium concentrations in a
      dose-dependent manner, whereas a saline bolus will not.

      Justification:

      Dexmedetomidine is a potent, centrally acting α-2 adrenoreceptor agonist with sympatholytic,
      sedative, amnestic, anxiolytic and analgesic effects, which properties make it popular for
      use in both pediatric anesthesia and intensive care. In 2013, dexmedetomidine was added to
      the "possible risk factor for torsades de pointes (TdP)" drug list on crediblemeds.org.
      Clinicians are currently advised to be vigilant about potential QT prolongation with
      dexmedetomidine, especially in patients with congenital long QT syndrome (LQTS). However,
      current evidence for dexmedetomidine-induced prolonged QT is sparse and somewhat
      contradictory, and the effect of dexmedetomidine on the Tp-e interval has yet to be reported
      in detail in adults or children. Another poorly defined pharmacodynamic effect of
      dexmedetomidine is its effect on blood glucose concentration. Theoretically, dexmedetomidine
      would be expected to cause hypoinsulinaemia and a resultant increase in blood glucose levels
      (hyperglycemia). Previous studies are in contrast to this however; with reports of
      hypoglycemia after large doses of the drug. Considering the use of dexmedetomidine in
      pediatric anesthesia, pediatric intensive care and its increasing use in the neonatal
      population, increased knowledge of the effect of dexmedetomidine on blood glucose would be
      valuable.

      Finally, hypokalemia is listed as a treatment-emergent adverse event occurring in >2% of
      adult patients receiving dexmedetomidine in long-term intensive care unit sedation studies.
      The effect of dexmedetomidine on serum potassium levels in healthy children has yet to be
      elucidated. Given that hypokalemia increases the risk of TdP, and that there is a possibility
      that dexmedetomidine may be torsadogenic, this effect is also worthy of investigation.

      In sum, the use of dexmedetomidine is associated with many clinical benefits, but its effects
      on indices of myocardial repolarization, as well as its effects on glucose and potassium
      metabolism, remain poorly understood and need to be better defined in order to use this drug
      safely and effectively.

      Objectives:

      The primary objective of this study is to investigate the effects of three different doses of
      dexmedetomidine (0.25/0.5/0.75 mcg/kg) on indices of myocardial repolarization (QTc and Tp-e
      intervals). As a secondary objective, this study will also sample blood glucose and potassium
      levels before and after dexmedetomidine administration to ascertain if there is any
      significant effect of a single bolus dose on blood glucose concentrations.

      Research Method:

      The investigators propose a randomized, single-blinded, 4-group comparative study to
      characterize the effects of different doses of dexmedetomidine on myocardial repolarization
      and blood glucose levels in healthy children undergoing elective surgery. The study-specific
      interventions will include giving a bolus of dexmedetomidine (0.25/0.5/0.75 mcg/kg; or 10mL
      saline) after induction of general anesthesia, recording two 12-lead ECGs (one before and one
      after dexmedetomidine administration), and taking three venous blood samples (one before and
      two after dexmedetomidine administration) to measure glucose and potassium. If the
      anesthetist would like to administer dexmedetomidine to a participant in the control (saline)
      group as part of their normal practice, they can do so after the study period is over (after
      the last blood sample).
    

Intervention name(s): Dexmedetomidine; Saline
Intervention type(s): Drug; Drug
Other intervention name(s): Precedex; 9% NaCl
Intervention MeSH terms: Dexmedetomidine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Basic Science
Keywords: changes in myocardial repolarization in healthy children