Intranasal Dexmedetomidine Premedication in Children

Phase 3

Completed

Conditions: Preoperative Sedation

Interventions: Drug: Midazolam
Drug: Dexmedetomidine

Registration Number: NCT02250703

Lead Sponsor: University of Mississippi Medical Center

Brief Summary: 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: 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 .

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 75

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Midazolam	Midazolam	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
Dexmedetomidine	Dexmedetomidine	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).

Primary Outcome Measures

Name	Time	Method
University of Michigan Sedation Scale	Day 0:Just before the patient will be brought to the operating room	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

Secondary Outcome Measures

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