The Effect of Age on the Median Effective Dose (ED50) of Intranasal Dexmedetomidine for Rescue Sedation Following Failed Sedation With Oral Chloral Hydrate During Magnetic Resonance Imaging

Study Overview
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Brief Summary
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Increasing evidences suggest that dexmedetomidine Pharmacokinetic are different in children. We performed a up-down sequential allocation study to determine the ED50 for rescue sedation following sedation failures in children and to investigate age-related differences in the rescue sedation with dexmedetomidine.

Detailed Description
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About 150 children who were not adequately sedated ( no evidence of adequate sedation within 30 min after administration of Initial dose of chloral hydrate) were stratified into four age groups as follows: 1-6 month, 7 -12 month, 13 -24 month, and 25-36 month. The intranasal dexmedetomidine dose was determined by the success or failure of rescue sedation achieved by the previous patients, according to Dixon's up-down sequential allocation method. Successful sedation was defined as a MOAA/S(modified Observer Assessment of Alertness and Sedation) of between 0 and 3. The EC50 were estimated from the up-and-down sequences using the method of Dixon and Massey and logistic regression. Patients' sedation status, sedation induction time, time to Wake up, blood pressure, heart rate, and oxygen saturation were recorded.

Conditions
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Aged, Drug, Dose-Response Relationship

Intervention / Treatment
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* Drug: intranasal dexmedetomidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 150 children of ASA physical status I or II, aged between 1 and 36 months, failed chloral hydrate sedation during MRI scanning, Exclusion Criteria: known allergy or hypersensitive reaction to drugs of this study, Weight greater than 20 kg or less than 4.5 kg, organ dysfunction, pneumonia, acute upper respiratory airway inflammation, preterm, cardiac arrhythmia and congenital heart disease.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 36 Months

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

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1-6 months (Group 1)<br>Subjects stratified into four groups according to age: 1-6 months (Group 1), 7-12 months (Group 2),13-24 months (Group 3), 26-36 months (Group 4). | Drug: intranasal dexmedetomidine<br>* Children who were not adequately sedated ( no evidence of adequate sedation within 30 min after administration of Initial dose of chloral hydrate) received a bolus of intranasal dexmedetomidine which adjusted by the Dixon up-and-down method for rescue sedation. The first child received 0.8mcg/Kg of intranasal dexmedetomidine dose (100mcg/ml), and the dose interval was set at 0.1mcg/Kg.<br>|
| Active Comparator: 7-12 months (Group 2)<br>Subjects stratified into four groups according to age: 1-6 months (Group 1), 7-12 months (Group 2),13-24 months (Group 3), 26-36 months (Group 4). | Drug: intranasal dexmedetomidine<br>* Children who were not adequately sedated ( no evidence of adequate sedation within 30 min after administration of Initial dose of chloral hydrate) received a bolus of intranasal dexmedetomidine which adjusted by the Dixon up-and-down method for rescue sedation. The first child received 0.8mcg/Kg of intranasal dexmedetomidine dose (100mcg/ml), and the dose interval was set at 0.1mcg/Kg.<br>|
| Active Comparator: 13-24 months (Group 3)<br>Subjects stratified into four groups according to age: 1-6 months (Group 1), 7-12 months (Group 2),13-24 months (Group 3), 26-36 months (Group 4). | Drug: intranasal dexmedetomidine<br>* Children who were not adequately sedated ( no evidence of adequate sedation within 30 min after administration of Initial dose of chloral hydrate) received a bolus of intranasal dexmedetomidine which adjusted by the Dixon up-and-down method for rescue sedation. The first child received 0.8mcg/Kg of intranasal dexmedetomidine dose (100mcg/ml), and the dose interval was set at 0.1mcg/Kg.<br>|
| Active Comparator: 25-36 months (Group 4)<br>Subjects stratified into four groups according to age: 1-6 months (Group 1), 7-12 months (Group 2),13-24 months (Group 3), 26-36 months (Group 4). | Drug: intranasal dexmedetomidine<br>* Children who were not adequately sedated ( no evidence of adequate sedation within 30 min after administration of Initial dose of chloral hydrate) received a bolus of intranasal dexmedetomidine which adjusted by the Dixon up-and-down method for rescue sedation. The first child received 0.8mcg/Kg of intranasal dexmedetomidine dose (100mcg/ml), and the dose interval was set at 0.1mcg/Kg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The median effect dose of intranasal dexmedetomidine | Sedation status was evaluated by a attending anesthesiologists every 5-10 min with a 6-point sedation scale, which was modified from the Modified Observer Assessment of Alertness and Sedation Scale (MOAA/S).successful sedation was defined as an MOAA/S of between 0 and 3 | up to 1 hours after MRI scaning | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sedation induction time | Successful sedation was defined as an MOAA/S of between 0 and 3, and sedation induction time was defined as the time from rescue drug administration to the onset of satisfactory sedation 0 Does not respond to a noxious stimulus Does not respond to mild prodding or shaking Responds only after mild prodding or shaking Responds only after name is called loudly orrepeatedly Lethargic response to name spoken in normal tone Appears asleep, but responds readily to namespoken in normal tone Appears alert and awake, responds readily to namespoken in normal tone | up to 30 min after rescue drug administration | 
| Wake -up time | Children were classified as awake if the MOAA/S was between 4 and 6. Wake -up time was defined as the time from successful sedation until the time that the child awoke | up to 4 hours after rescue drug administration |