Intranasal Dexmedetomidine Premedication in Children

Study Overview
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Brief Summary
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BACKGROUND INFORMATION AND RATIONALE Pediatric patients scheduled for dental procedures under general anesthesia can have significant anxiety before the procedure. They are commonly pre medicated to minimize distress and to facilitate a smooth induction of anesthesia. Oral Midazolam at 0.5mg/kg dose is more widely used for this purpose . However the commonly used maximum dose is up to 15mg. It also has many limitations such as paradoxical reaction, increased incidence of emergence delirium and negative postoperative behavior changes . Intranasal dexmedetomidine has been used an effective and safe alternative premedication to oral midazolam in children. At a dose of 2micrograms/kg, intranasal dexmedetomidine as premedication resulted in excellent sedation in children aged 5-8yrs with no adverse hemodynamic effects. It has other advantages such as providing analgesia and facilitating smooth emergence from anesthesia. The goal of this study is to find out if intranasal dexmedetomidine is a superior alternative as premedication to oral midazolam in children weighing more than 20kg undergoing general anesthesia for dental rehabilitation.

Detailed Description
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After Institutional Review Board (IRB) approval and written informed consent from patients' parents or legally authorized representative, 80 children older than 5yrs and weighing more than 20kg, ASA physical status 1 or 2, scheduled for elective dental rehabilitation with general anesthesia will be enrolled in this prospective randomized double blinded study. Exclusion criteria include known allergy or hypersensitivity to midazolam or dexmedetomidine, uncorrected congenital heart disease or history of cardiac arrhythmia, children at risk for airway obstruction (OSA or cranio facial syndrome) and pregnant minors Patients will be randomly assigned to one of two groups M (midazolam) or D (dexmedetomidine) using computer-generated numbers in sealed envelopes. All the patients will be brought to their pre-op room and premedicated at least 30 min before induction of anesthesia. In M group, patients will be given oral midazolam 0.5mg/kg upto maximum dose of 15mg (5mg/ml parenteral preparation) mixed with flavored syrup. In D group, patients will be given intranasal dexmedetomidine 2mcg/kg upto maximum dose of 100mcg prepared from 100mcg/ml parenteral preparation (Hospira R). The drug will be administered using a intranasal mucosal administration device (LMA MAD NasalTM). Atomized nasal medications offer rapid absorption across mucosal membranes to the blood stream avoiding first-pass metabolism. Parents will be present in the room during premedication. The Anesthesia personnel involved in the care of the patient (MD or CRNA) will prepare and administer all study drugs. All patients will be continuously monitored in the holding area with pulse oximetry and blood pressure monitor. HR, SPO2 and BP will be recorded every 15min after administration of premedication until transfer to the OR. Emergency medications including atropine and epinephrine will be immediately available in the pre-op holding area. Oral midazolam has been used with very little effect on hemodynamic parameters. Although intranasal dexmedetomidine can decrease HR and BP, it has been used at the dose of 2mcg/kg without any adverse hemodynamic effect . Any intervention needed to treat drop in HR (<50) and BP (sys BP <60) after the drug administration will be recorded. Behavior of the children at the time of premedication will be documented ( easy or difficult). Any unwanted effects during administration such as spitting or vomiting of oral drug and pain or irritation from nasal administration will be documented. The dental resident blinded to study drug administration will do the pre-operative sedation status and acceptance of mask induction. Sedation status will be assessed using University of Michigan sedation scale (UMSS)on separation from parents and at induction after moving to the OR table. Acceptance of mask induction will be documented on a 4-point scale. Standard ASA monitors will be applied before induction of anesthesia. All patients will undergo mask induction with O2/N2O/Sevo. An intravenous line will be inserted and secured. Both nostrils will be prepped nasal drops and tips of tracheal tubes covered with red rubber to minimize bleeding. Nasal intubation will be performed with direct laryngoscopy and McGill's forceps. Appropriate size cuffed tracheal tubes will be inserted and secured after additional IV medications with propofol 2-3mg/kg and fentanyl 1-2mcg/kg. Anesthesia will be maintained with O2/Sevo, IV morphine 0.05 to 0.1mg/kg and IV toradol 0.5mg/kg (if there is no allergy or contraindication to morphine or toradol) After the completion of procedure, patients will be extubated in the operating room and brought to recovery room and allowed to wake up slowly in the recovery position. PACU nurses will evaluate Behavior at awakening using four-point wake up score (9,20). Patients will also be asked if they remember mask induction (yes or no) when they are ready for discharge. Incidence of nausea, vomiting, shivering will be documented in PACU. Time spent in phase 1 recovery room will also be recorded .

Official Title
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Comparing Intranasal Dexmedetomidine With Oral Midazolam as Premedication for Older Children Undergoing General Anesthesia for Dental Rehabilitation

Conditions
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Preoperative Sedation

Intervention / Treatment
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* Drug: Midazolam
* Drug: Dexmedetomidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children older than 5yrs and weighing more than 20kg , who are scheduled for ambulatory dental rehabilitation at Batson operating rooms. ASA classification 1 or 2 Exclusion Criteria Known allergy to midazolam, dexmedetomidine,morphine, fentanyl, sevoflurane and propofol. uncorrected congenital heart disease or history of cardiac arrhythmia, children at risk for airway obstruction (OSA or cranio facial syndrome), pregnant minors

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Midazolam<br>In M group, patients will be given oral midazolam 0.5mg/kg upto maximum dose of 15mg (5mg/ml parenteral preparation) mixed with flavored syrup as premedication | Drug: Midazolam<br>* oral midazolam 0.5mg/kg upto maximum dose of 15mg<br>|
| Experimental: Dexmedetomidine<br>In D group, patients will be given intranasal dexmedetomidine 2mcg/kg upto maximum dose of 100mcg prepared from 100mcg/ml parenteral preparation (Hospira R) . The drug will be administered using a intranasal mucosal administration device (LMA MAD NasalTM). | Drug: Dexmedetomidine<br>* intranasal dexmedetomidine 2mcg/kg upto maximum dose of 100mcg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| University of Michigan Sedation Scale | Level of sedation at separation from parents and at the time of mask induction will be measured on a scale of 0 to 4 (University of Michigan Sedation Scale) University of Michigan Sedation Scale: 0 -Awake/Alert 1 -Minimally Sedated: Tired/sleepy, appropriate response to verbal conversation and/or sounds. 2- Moderately Sedated: Somnolent/sleeping, easily aroused with light tactile stimulation. 3 - Deeply Sedated: Deep sleep, arousable only with significant physical stimulation. 4 - Unarousable Moderately and Deeply sedated: Satisfactory Awake, minimally sedate, unarousable: Unsatisfactory | Day 0:Just before the patient will be brought to the operating room | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acceptance of Mask Induction | on a scale of 1 to 4 excellent( cooperative) good( slight fear, easily calmed) fair ( moderate fear, not calmed with reassurance) Poor( agitated, terrified) 1 and 2 are considered satisfactory 3 and 4 are considered unsatisfactory | Day 0: At the time when anesthesia is induced | 
| Wake up Behavior | assessed in post anesthesia recovery unit after the procedure on a scale of 1o 4 calm not calm but easily calmed moderately agitated or restless combative/disoriented 1 and 2 are considered satisfactory 3 and 4 are considered unsatisfactory | Day 0: At the end of surgery when the patient recovers from anesthesia | 
| Presence of Amnesia to Mask Induction | Yes or No (if the patient remembers mask induction) | Day 0: at the time of discharge of the patient from the recovery room | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Premedication