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

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.

Study Overview

• Status: Completed
• Conditions: Aged; Drug; Dose-Response Relationship
• Intervention / Treatment: Drug: intranasal dexmedetomidine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Department of Anesthesiology of Guangzhou Women and Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1-6 months (Group 1); 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; 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.
Active Comparator: 7-12 months (Group 2); 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; 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.
Active Comparator: 13-24 months (Group 3); 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; 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.
Active Comparator: 25-36 months (Group 4); 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; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
heart rate	changes in heart rates at the baseline, before and 15 , 60, 75, 90 min after rescue drug administration	baseline, before and 15 , 60, 75, 90 min after rescue drug administration
non-invasive systolic blood pressure	changes in the non-invasive systolic blood pressure at the baseline, before and 15 , 30, 60, 75, 90 min after rescue drug administration	baseline, before and 15 , 60, 75, 90 min after rescue drug administration
Oxyhemoglobin desaturation	Significant Oxyhemoglobin desaturation was defined as<94%	baseline and four hours after rescue medicine administration

Collaborators and Investigators

• Sponsor: Guangzhou Women and Children's Medical Center

Publications and helpful links

General Publications

• Zhang W, Fan Y, Zhao T, Chen J, Zhang G, Song X. Median Effective Dose of Intranasal Dexmedetomidine for Rescue Sedation in Pediatric Patients Undergoing Magnetic Resonance Imaging. Anesthesiology. 2016 Dec;125(6):1130-1135. doi: 10.1097/ALN.0000000000001353.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: September 29, 2014
• First Submitted That Met QC Criteria: September 29, 2014
• First Posted (Estimate): October 1, 2014

Study Record Updates

• Last Update Posted (Estimate): March 29, 2016
• Last Update Submitted That Met QC Criteria: March 26, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: WZhang-02