Clinical trial NCT02353169: The Effects of Dexmedetomidine on the Heart Beat During Elective Surgery in Children
Official title: The Effects of Dexmedetomidine on Myocardial Repolarization in Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Myocardial Repolarization
Healthy
Keywords: changes in myocardial repolarization in healthy children
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2015-02-02
Enrollment: 64
Sex: ALL
Minimum age (years): 3
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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).

Eligibility criteria: Inclusion Criteria:

* ASA Physical Status I-II
* Age 3 to 10yrs
* Elective surgical procedure requiring general anesthesia
* Use of dexmedetomidine acceptable to the staff anesthesiologist
* Un-premedicated
* Ability to read and understand English (parent/legal guardian(s) and child)

Exclusion Criteria:

* Long QT syndrome (LQTS)
* Cardiac disease or rhythm abnormalities
* Family history of LQTS or abnormal cardiac conduction
* Currently taking medications known to prolong QT
* Currently taking medications known to predispose to hypokalemia
* Known hypersensitivity to dexmedetomidine or other study medication
* Weight \< 5th centile or \> 95th centile for age
* Previously diagnosed hypokalemia
* Impaired renal or liver function
* Pre-operative anxiety requiring sedatives or opioids
* Refusal to participate

Primary outcomes:
measure: Myocardial Repolarization (QTc and TP-e Intervals) 1min After Intervention
timeFrame: 60 seconds post-intervention
Secondary outcomes:
measure: Blood Glucose Levels at 15min and 30min Post-intervention
timeFrame: over 30 minutes post-intervention
measure: Blood Potassium Levels at 15min and 30min Post-intervention
timeFrame: over 30 minutes post-intervention
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: BC Children's Hospital - Department of Anesthesia
state: British Columbia
Study officials:
affiliation: BC Children's Hospital, Department of Anesthesia
name: Simon Whyte, MBBS, FRCA
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gorges M, Poznikoff AK, West NC, Brodie SM, Brant RF, Whyte SD. Effects of Dexmedetomidine on Blood Glucose and Serum Potassium Levels in Children Undergoing General Anesthesia: A Secondary Analysis of Safety Endpoints During a Randomized Controlled Trial. Anesth Analg. 2019 Oct;129(4):1093-1099. doi: 10.1213/ANE.0000000000004154.
citation: Gorges M, Sherwin ED, Poznikoff AK, West NC, Brodie SM, Whyte SD. Effects of Dexmedetomidine on Myocardial Repolarization in Children Undergoing General Anesthesia: A Randomized Controlled Trial. Anesth Analg. 2019 Oct;129(4):1100-1108. doi: 10.1213/ANE.0000000000004135.