Remifentanil in Children With Obstructive Sleep Apnea

Study Overview
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Brief Summary
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This investigation tested the hypothesis that children with obstructive sleep apnea have an increased pharmacodynamic sensitivity to the miotic and respiratory depressant effects of the prototypic μ-opioid agonist remifentanil.

Official Title
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The Pharmacokinetic and Pharmacodynamics Profiles of Remifentanil in Children With Obstructive Sleep Apnea.

Conditions
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Obstructive Sleep Apnea

Intervention / Treatment
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* Drug: Remifentanil Infusion


Participation Criteria
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Eligibility Criteria
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OSA Group: Inclusion Criteria: 8-14 years old ASA physical status 1 or 2 undergoing tonsillectomy or tonsillectomy and adenoidectomy for known obstructive sleep apnea Exclusion Criteria: Inability to cooperate with study requirements (IV placement, sitting quietly, wearing goggles, etc.) Control (Non-OSA) Group: Inclusion Criteria: 8-14 years old ASA physical status 1 or 2 no known obstructive sleep apnea presenting for any procedure requiring general anesthtic Exclusion Criteria: Inability to cooperate with study requirements (IV placement, sitting quietly, wearing goggles, etc.)

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel group study comparing patients with obstructive sleep apnea undergoing tonsillectomy or tonsillectomy and adenoidectomy to controls with no history of obstructive sleep apnea undergoing general anesthesia for any procedure. The study will be conducted in the patient's preoperative holding area room. Two intravenous catheters will be placed, one for a remifentanil infusion and one for blood draws to measure the blood concentration of remifentanil. Patients will have standard ASA monitors placed with vital signs monitored on a portable monitor, and a remifentanil infusion will be started. Blood draws will be taken at seven time points: zero, one, two, four, six, ten and fifteen minutes. Concomitantly, recordings of end tidal CO2, respiratory rate, and pupil diameter will be made at the seven time points.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: OSA Group<br>a) Children 8-14 years old, b) ASA physical status 1or 2, c) undergoing tonsillectomy or tonsillectomy and adenoidectomy for known obstructive sleep apnea | Drug: Remifentanil Infusion<br>* 15 minute remifentanil Infusion of either 0.05, 0.1, 0.15 or 0.2 mcg/kg/min<br>|
| Active Comparator: Control (non-OSA) Group<br>a) Children 8-14 years old, b) ASA physical status 1or 2, c) no known obstructive sleep apnea presenting for any procedure requiring general anesthetic | Drug: Remifentanil Infusion<br>* 15 minute remifentanil Infusion of either 0.05, 0.1, 0.15 or 0.2 mcg/kg/min<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in end-expired carbon dioxide from baseline over time - OSA Group | End-expired carbon dioxide monitoring using bedside monitoring | Approximately 1 hour before surgery - Measurements taken at 0, 1, 2, 4, 6, 10 & 15 minutes following remefentanil infusion | 
| Change in end-expired carbon dioxide from baseline over time - Control (non-OSA) Group | End-expired carbon dioxide monitoring using bedside monitoring | Approximately 1 hour before surgery - Measurements taken at 0, 1, 2, 4, 6, 10 & 15 minutes following remefentanil infusion | 
| Change in respiratory rate from baseline over time - OSA Group | Respiratory monitoring was performed using nasal cannula | Approximately 1 hour before surgery - Measurements taken at 0, 1, 2, 4, 6, 10 & 15 minutes following remefentanil infusion | 
| Change in respiratory rate from baseline over time - Control (non-OSA) Group | Respiratory monitoring was performed using nasal cannula | Approximately 1 hour before surgery - Measurements taken at 0, 1, 2, 4, 6, 10 & 15 minutes following remefentanil infusion | 
| Change in pupil diameter from baseline over time - OSA Group | Dark adapted infrared pupillometry performed using binocular infrared pupilometer mounted in light occlusive goggles sampling at 100 Hz. | Approximately 1 hour before surgery - Measured continuously and averaged into 10-s bins following remefentanil infusion | 
| Change in pupil diameter from baseline over time - Control (non-OSA) Group | Dark adapted infrared pupillometry performed using binocular infrared pupilometer mounted in light occlusive goggles sampling at 100 Hz. | Approximately 1 hour before surgery - Measured continuously and averaged into 10-s bins following remefentanil infusion | 
| Remifentanil plasma concentration - OSA Group | 3ml blood draw | Approximately 1 hour before surgery - Blood draws at 0, 1, 2, 4, 6, 10 & 15 minutes following remefentanil infusion | 
| Remifentanil plasma concentration - Contro (non-OSA) Group | 3ml blood draw | Approximately 1 hour before surgery - Blood draws at 0, 1, 2, 4, 6, 10 & 15 minutes following remefentanil infusion |