ED50 and ED95 of Intranasal Dexmedetomidine in Pediatric Patients Undergoing Transthoracic Echocardiography Study
Study Details
Study Description
Brief Summary
The median effective dose (ED50) and ED95 of intranasal dexmedetomidine as a single bolus have not been described for sedation in children undergoing transthoracic echocardiography (TEE) study. This information is important to compare agents and to determine the most effective sedative dose. The investigators performed a two-stage study to determine the ED50 and the ED95 of intranasal dexmedetomidine to investigate age-related differences in participants undergoing transthoracic echocardiography study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
The investigators performed a two-stage study to determine the ED50 and the ED95 of intranasal dexmedetomidine in children undergoing transthoracic echocardiography study. In phase 1, 120 participants were randomized in a Dixon-Massey study to describe the minimum local sedative dose. In phase 2, a further 160 participants were randomly allocated to receive sedation with doses in the upper dose-response range to define the ED95
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: 1-6 months (Group 1)
|
Drug: intranasal dexmedetomidine
Phase 1, Children received a bolus of intranasal dexmedetomidine which adjusted by the "Dixon up-and-down method for TEE study. The first child received 2.5 mcg/kg of intranasal dexmedetomidine dose (100mcg/ml), and the dose varied by 0.1 mcg/kg according to the up-and-down method Phase 2 was a dose-escalation study. After interim analysis of the phase 1 results, four dose levels above the calculated ED50 were defined. Dose spacing was set at 0.25 mcg/kg of intranasal dexmedetomidine consistent with the re-estimated standard deviation (SD).
|
| Active Comparator: 7-12 months (Group 2)
|
Drug: intranasal dexmedetomidine
Phase 1, Children received a bolus of intranasal dexmedetomidine which adjusted by the "Dixon up-and-down method for TEE study. The first child received 2.5 mcg/kg of intranasal dexmedetomidine dose (100mcg/ml), and the dose varied by 0.1 mcg/kg according to the up-and-down method Phase 2 was a dose-escalation study. After interim analysis of the phase 1 results, four dose levels above the calculated ED50 were defined. Dose spacing was set at 0.25 mcg/kg of intranasal dexmedetomidine consistent with the re-estimated standard deviation (SD).
|
| Active Comparator: 13-18 months (Group 3)
|
Drug: intranasal dexmedetomidine
Phase 1, Children received a bolus of intranasal dexmedetomidine which adjusted by the "Dixon up-and-down method for TEE study. The first child received 2.5 mcg/kg of intranasal dexmedetomidine dose (100mcg/ml), and the dose varied by 0.1 mcg/kg according to the up-and-down method Phase 2 was a dose-escalation study. After interim analysis of the phase 1 results, four dose levels above the calculated ED50 were defined. Dose spacing was set at 0.25 mcg/kg of intranasal dexmedetomidine consistent with the re-estimated standard deviation (SD).
|
| Active Comparator: 19-24 months (Group 4)
|
Drug: intranasal dexmedetomidine
Phase 1, Children received a bolus of intranasal dexmedetomidine which adjusted by the "Dixon up-and-down method for TEE study. The first child received 2.5 mcg/kg of intranasal dexmedetomidine dose (100mcg/ml), and the dose varied by 0.1 mcg/kg according to the up-and-down method Phase 2 was a dose-escalation study. After interim analysis of the phase 1 results, four dose levels above the calculated ED50 were defined. Dose spacing was set at 0.25 mcg/kg of intranasal dexmedetomidine consistent with the re-estimated standard deviation (SD).
|
Outcome Measures
Primary Outcome Measures
- The ED50 doses for intranasal dexmedetomidine [up to 0.5 hours after transthoracic echocardiography]
Phase 1: The starting dose of dexmedetomidine was 2.5 mcg/kg. These doses varied by 0.1 mcg/kg, according to the up-and-down method 18. If the detected MOAA/S score was >3 within 45 minutes after intranasal administration, or clinically adequate diagnostic-quality images could not be acquired, sedation was considered a failure; and the dexmedetomidine dose was increased by 0.1 mcg/kg in the next patient of the same age group. In contrast, if the detected MOAA/S score was ≤3 and the acquisition of clinically adequate diagnostic-quality images was possible, the sedation was considered successful; and the dexmedetomidine dose was decreased by 0.1 mcg/kg in the next patient o
- The ED95 doses for intranasal dexmedetomidine [up to 0.5 hours after transthoracic echocardiography]
Phase 2 was a dose-escalation study. After interim analysis of the phase 1 results, four dose levels above the calculated ED50 were defined. Dose spacing was set at 0.3 mcg/kg of intranasal dexmedetomidine consistent with the re-estimated standard deviation (SD). Defined levels were set at about 2.5, 2.75, 3.0, and 3.25 mcg/kg of intranasal dexmedetomidine. Criteria for success and failure were identical to those in phase 1. Successful sedation was defined as a MOAA/S score between 0-3 and allowed the acquisition of clinically adequate diagnostic-quality images, while failure was defined as a MOAA/S score >3 within 45 minutes or clinically adequate diagnostic-quality images could not be acquired
- Score of physical movement [up to 0.5 hours after transthoracic echocardiography]
Movement score was recorded by sonographers who were blinded to the sedative regimen. No movement Occasional, slight movement Frequent, slight movement Vigorous movement limited to extremities Vigorous movement, including torso and head
Secondary Outcome Measures
- sedation induction time [up to 2 hours after drug administration]
Successful sedation was defined as an MOAA/S of between 0 and 3, and sedation induction time was defined as the time from drug administration to the onset of satisfactory sedation
- Wake -up time [up to 2 hours after drug administration]
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
Other Outcome Measures
- heart rate [up to 3 hours after drug administration]
Bradycardia was defined as a reduction in heart rate more than 20% from the baseline values
- Oxyhemoglobin desaturation [up to 3 hours after drug administration]
Significant Oxyhemoglobin desaturation was defined as < 90%.
- non-invasive systolic blood pressure [up to 3 hours after drug administration]
Hypotension was defined as a reduction in systolic blood pressure more than 20% from the baseline values
Eligibility Criteria
Criteria
Inclusion Criteria:
- Children, aged between one and 24 months. classified as (American Society of Anesthesiologists) ASA physical status I or II, undergoing TEE were enrolled in the study.
Exclusion Criteria:
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Known allergy or hypersensitive reaction to dexmedetomidine
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Organ dysfunction, and significant developmental delays or behavior problems
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Cardiac arrhythmia
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Known. acyanotic congenital heart disease or children after cardiac interventional procedures for follow-up examination.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Anesthesiology of Guangzhou Women and Children's Medical Center | Guangzhou | Guangdong | China | 510000 |
Sponsors and Collaborators
- Guangzhou Women and Children's Medical Center
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Wzhang03