Clinical trial NCT04301895: Pupillary Unrest in Ambient Light, and Relationship to Opioid-Induced Respiratory Depression
Official title: Pupillary Unrest in Ambient Light, and Relationship to Opioid-Induced Respiratory Depression in Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Opioid; Intoxication, Perception Disturbance (Acute)
Acute Pain
Overdose of Opiate
Respiratory Depression
Safety Issues
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2020-03-10
Enrollment: 20
Sex: ALL
Minimum age (years): 20
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Each subject is his/her own control.
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

* Healthy
* Able to provide informed consent

Exclusion Criteria:

* Active substance use disorder
* Prior opioid use disorder
* Opioid use within 30 days.

Primary outcomes:
measure: Impact of environmental stimulation on decline in oxygen saturation to ≤ 90%.
timeFrame: 35 minutes
measure: Impact of environmental stimulation on CO2 increase of 15% or more above baseline.
timeFrame: 35 minutes
measure: Correlation between estimated opioid concentration and deviation in pupillary measurement.
timeFrame: 35 minutes
Secondary outcomes:
measure: Impact of environmental stimulation on opioid-related deviations in pupillary measurements.
timeFrame: 35 minutes
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
Study officials:
affiliation: Professor of Anesthesia
name: Rachel Eshima McKay, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: McKay RE, Kohn MA, Larson MD. Pupillary unrest, opioid intensity, and the impact of environmental stimulation on respiratory depression. J Clin Monit Comput. 2022 Apr;36(2):473-482. doi: 10.1007/s10877-021-00675-3. Epub 2021 Mar 2.