Remifentanil in Children With Obstructive Sleep Apnea (ROSA)

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

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.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Drug: Remifentanil Infusion

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 14 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: OSA Group; 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; 15 minute remifentanil Infusion of either 0.05, 0.1, 0.15 or 0.2 mcg/kg/min
Active Comparator: Control (non-OSA) Group; 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; 15 minute remifentanil Infusion of either 0.05, 0.1, 0.15 or 0.2 mcg/kg/min

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine

Publications and helpful links

General Publications

• Brown KA. Outcome, risk, and error and the child with obstructive sleep apnea. Paediatr Anaesth. 2011 Jul;21(7):771-80. doi: 10.1111/j.1460-9592.2011.03597.x. Epub 2011 May 3.
• Marcus CL, Brooks LJ, Draper KA, Gozal D, Halbower AC, Jones J, Schechter MS, Ward SD, Sheldon SH, Shiffman RN, Lehmann C, Spruyt K; American Academy of Pediatrics. Diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics. 2012 Sep;130(3):e714-55. doi: 10.1542/peds.2012-1672. Epub 2012 Aug 27.
• Bhattacharyya N, Lin HW. Changes and consistencies in the epidemiology of pediatric adenotonsillar surgery, 1996-2006. Otolaryngol Head Neck Surg. 2010 Nov;143(5):680-4. doi: 10.1016/j.otohns.2010.06.918.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Actual): October 31, 2017
• Study Completion (Actual): October 31, 2017

Study Registration Dates

• First Submitted: May 16, 2019
• First Submitted That Met QC Criteria: May 16, 2019
• First Posted (Actual): May 22, 2019

Study Record Updates

• Last Update Posted (Actual): March 12, 2020
• Last Update Submitted That Met QC Criteria: March 10, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Remifentanil
• Other Study ID Numbers: 201504056

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes