Pupillary Unrest in Ambient Light, and Relationship to Opioid-Induced Respiratory Depression

Study Overview
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Brief Summary
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Volunteers will receive a weight-based opioid (remifentanil) infusion for 10 minutes. In the first run, serial pupillary measurements (pupillary unrest, pupil diameter) will be taken at baseline, and at 2.5-minute intervals during the infusion and a 25-minute recovery period afterwards. After a washout period, the experiment will be repeated in each subject (second run). The two runs differ only by presence versus absence of verbal interaction.

Detailed Description
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Healthy volunteers aged 20-55 will receive a weight-based opioid (remifentanil) infusion for 10 minutes. Vital signs including SpO2, transcutaneous CO2, and respiratory rate will be continuously measured. In the first run, serial pupillary measurements (pupillary unrest, pupil diameter) will be taken at baseline, and at 2.5-minute intervals during the infusion and a 25-minute recovery period afterwards. After a washout period, the experiment will be repeated in each subject (second run). The two runs differ only by presence of ongoing verbal interaction versus complete avoidance of verbal interaction. Incidence of respiratory depression will be compared in the two protocols with or without verbal interaction. Correlation between pupil diameter and pupillary unrest with estimated opioid concentrations will be determined by regression. Difference between pupil measurement versus opioid concentration regressions will be compared by chi2.

Official Title
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Pupillary Unrest in Ambient Light, and Relationship to Opioid-Induced Respiratory Depression in Volunteers

Conditions
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Opioid; Intoxication, Perception Disturbance (Acute), Acute Pain, Overdose of Opiate, Respiratory Depression, Safety Issues

Intervention / Treatment
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* Behavioral: Continuous conversational interaction
* Drug: Remifentanil infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Able to provide informed consent Exclusion Criteria: Active substance use disorder Prior opioid use disorder Opioid use within 30 days.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Each subject is his/her own control.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Interactive<br>Subject will be asked to continually interactive with the investigators, answering a series of standard questions during the remifentanil infusion and recovery periods. | Behavioral: Continuous conversational interaction<br>* Maintaining continuous conversation, requiring that the subject answer questions and engage in discussion without interruption.<br>* Other names: Environmental stimulation;Drug: Remifentanil infusion<br>* 10 minute remifentanil infusion<br>|
| Other: Non-interactive<br>All verbal interaction will be avoided and extraneous sounds will be eliminated from the environment during the remifentanil infusion and recovery periods. | Drug: Remifentanil infusion<br>* 10 minute remifentanil infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of environmental stimulation on decline in oxygen saturation to ≤ 90%. | Conversational interaction and oxygen saturation measured by pulse oximeter. | 35 minutes | 
| Impact of environmental stimulation on CO2 increase of 15% or more above baseline. | Conversational interaction and CO2 measured by transcutaneous sensor. | 35 minutes | 
| Correlation between estimated opioid concentration and deviation in pupillary measurement. | Relationship of opioid concentration to pupillary unrest, measured by the pupillometer | 35 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of environmental stimulation on opioid-related deviations in pupillary measurements. | Impact of conversational interaction on degree of decline in pupillary unrest as measured by the pupillometer. | 35 minutes |