The Effects of Dexmedetomidine on Intravenous Anesthetic Requirements for Children Undergoing Dental Procedures

Study Overview
=================
Brief Summary
-----------------
The investigators propose to determine the propofol and remifentanil sparing effects of a single dose of dexmedetomidine in the dental population. The investigators plan to do this by performing a blinded study with 4 test groups (3 experimental and 1 control), using BIS monitoring to titrate TIVA infusion to an acceptable depth of anesthesia.

Detailed Description
-----------------
Purpose: To determine an optimal dose of dexmedetomidine for its anesthetic sparing effect, without extending post-operative stay. Hypothesis: The investigators hypothesize that dexmedetomidine will cause a clinically significant reduction of 30% in the amount of propofol and remifentanil required to maintain adequate depth of anesthesia, as monitored through the Bispectral Index. Justification: The dose-sparing effect of dexmedetomidine on TIVA requirements and the dose-response relationship between dexmedetomidine and TIVA dosing regimens has not been explored in young children. This study will have many relevant applications to many areas of pediatric anesthesia practice, such as craniofacial and neurosurgery, sedation techniques in diagnostic and interventional radiology, out of OR sedation, and in all young children in whom minimizing anesthesia exposure is increasingly sought given possible concerns over the long term neurocognitive effects of surgery and anesthesia in early life. Objectives: To investigate the dose-sparing effect on a propofol/remifentanil infusion of bolus doses of dexmedetomidine and to characterize the dose-response relationship between dexmedetomidine doses and TIVA dose reduction. Research Design: The investigators propose a randomized, 4-group comparative study to characterize the effects of different bolus doses of dexmedetomidine on the infusion requirements of propofol and remifentanil. The study-specific interventions will include a bolus of dexmedetomidine (or placebo) at induction of anesthesia, and maintenance of anesthesia, titrated to a Bispectral index of 50-60, with propofol and remifentanil infusions. Statistical Analysis: Standard statistical analysis will be undertaken using R Foundation for Statistical Computing, Vienna, Austria). Summary data will be tabulated and presented as median (IQR). Mean infusion rates of propofol and remifentanil will be compared between groups using Wilcoxon signed-rank test, with 95% confidence intervals obtained by the Hodges-Lehmann estimator. Dose (in mcg/kg) of additional opioids given in PACU will be tabulated and compared using Fisher's exact test. Bonferroni corrections will be applied as appropriate whenever multiple comparisons are performed.

Official Title
-----------------
Anesthetic Sparing Effect of Dexmedetomidine During TIVA With Propofol and Remifentanil for Children Undergoing Dental Procedures

Conditions
-----------------
Anesthetic Sparing

Intervention / Treatment
-----------------
* Drug: Dexmedetomidine
* Drug: Normal saline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ASA 1-2 Elective dental surgery Planned general anesthesia with TIVA Age 2-10 years Exclusion Criteria: General anesthesia with inhalation induction Documented seizure disorder Cardiac disease Cardiac rhythm abnormalities Chronic hypertension Weight < 5th centile or > 95th centile for age Pre-operative administration of anxiolytics (such as benzodiazepines or opioid analgesics) Hypersensitivity to dexmedetomidine or any other study medication

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 10 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Saline bolus<br>10mL normal saline solution administered intravenously over 60 seconds starting after intubation. | Drug: Normal saline<br>* Single dose normal saline administered over 60 seconds post-induction.<br>|
| Experimental: Dexmedetomidine 0.25 mcg/kg<br>0.25 mcg/kg dexmedetomidine diluted with normal saline to a 10mL volume, administered intravenously over 60 seconds starting after intubation. | Drug: Dexmedetomidine<br>* Single dose dexmedetomidine administered over 60 seconds post-induction.<br>* Other names: Precedex;|
| Experimental: Dexmedetomidine 0.50 mcg/kg<br>0.50 mcg/kg dexmedetomidine diluted with normal saline to a 10mL volume, administered intravenously over 60 seconds starting after intubation. | Drug: Dexmedetomidine<br>* Single dose dexmedetomidine administered over 60 seconds post-induction.<br>* Other names: Precedex;|
| Experimental: Dexmedetomidine 1.00 mcg/kg<br>1.00 mcg/kg dexmedetomidine diluted with normal saline to a 10mL volume, administered intravenously over 60 seconds starting after intubation. | Drug: Dexmedetomidine<br>* Single dose dexmedetomidine administered over 60 seconds post-induction.<br>* Other names: Precedex;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Propofol and remifentanil sparing | Propofol and remifentanil sparing as measured by time-averaged, total administered doses of propofol (mg/kg) and remifentanil (mcg/kg) compared to the placebo group. | Through length of procedure, an average of 1.5 hours | 
| Propofol and remifentanil infusion rate reduction | Change in infusion rates of propofol and remifentanil (in micrograms/kg/min), measured over time compared to the placebo group. | Through length of procedure, an average of 1.5 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PACU sedation | Sedation will be scored from 0 (alert) to 4 (unarousable) using the University of Michigan sedation score (UMSS) at 10, 20, and 30 minutes post discontinuation of the infusions. | 30min post-procedure | 
| PACU pain scores | Pain will be scored from 0 (no pain) to 10 (severe pain), using the FLACC pain scale for ages 2-7 and the FACES pain scale for ages 8-10, and total fentanyl doses in mcg/kg given in the Post Anesthetic Care Unit will be recorded. | 30min post-procedure | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Dexmedetomidine