Pupillary Unrest as an Indicator of Central Opioid Effect in Subjects 40-60 Years of Age

Purpose

This study will establish the relationship between magnitude of opioid exposure and a pupillary measure referred to as PUAL (pupillary unrest in ambient light), in subjects aged 40-60. Previous investigation demonstrated that loss of PUAL was a sensitive, discriminative indicator of opioid toxicity and respiratory depression among subjects aged 20-40 years old. Population data indicate that pupil size and PUAL decline slightly with age. The investigators will explore whether PUAL proves to be a sensitive indicator of opioid exposure and respiratory depression in this older group.

Conditions

  • Opioid Toxicity
  • Pupillary Miosis
  • Respiratory Depression

Eligibility

Eligible Ages
Between 40 Years and 60 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  • Healthy, BMI < 35 kg/m2

Exclusion Criteria

  • current or recent opioid use - opioid or other substance use disorder - known or suspected OSA or sleep disordered breathing - ischemic heart disease, heart failure or symptomatic arrhythmia history - ocular disease or previous eye surgery - active use of alpha adrenergic blockers, anticholinergic medications, - active use of antidepressant or mood stabilizing medications - active use of phosphodiesterase inhibitors - use of stimulant or appetite suppressant medications - active use of antihypertensive or antiarrhythmic medications - use of topical eye medications.

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover Assignment
Primary Purpose
Diagnostic
Masking
None (Open Label)
Masking Description
The investigator determining the PUAL will be blinded to the opioid level concurrent with the measurement.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Noninteractive, then Interactive
Participants undergo the infusion under noninteractive conditions, followed by a second drug infusion under interactive conditions.
  • Drug: Remifentanil Hydrochloride
    Infusion of 0.2 µg/k/m for 5 minutes, the 0.3 µg/k/m for 5 minutes. Pupillary measurements will be taken at baseline and every 2.5 minutes during the 10-minute infusion and 25-minute recovery period.
  • Device: Pupillometry measurement
    The pupil will be examined with the pupillometer at regular intervals, before during and after the opioid infusion
Experimental
Interactive, then Noninteractive
Participants undergo the infusion under interactive conditions, followed by a second drug infusion under noninteractive conditions.
  • Drug: Remifentanil Hydrochloride
    Infusion of 0.2 µg/k/m for 5 minutes, the 0.3 µg/k/m for 5 minutes. Pupillary measurements will be taken at baseline and every 2.5 minutes during the 10-minute infusion and 25-minute recovery period.
  • Device: Pupillometry measurement
    The pupil will be examined with the pupillometer at regular intervals, before during and after the opioid infusion

Recruiting Locations

More Details

Status
Recruiting
Sponsor
University of California, San Francisco

Study Contact

Rachel Eshima McKay, MD
415-502-1715
rachel.eshima@ucsf.edu

Detailed Description

Healthy volunteer subjects aged 40-60 will receive a standardized weight-based 10-minute remifentanil infusion protocol to achieve a peak estimated remifentanil effect site concentration of approximately 6 ng/mL. Pupillary measures will be taken at baseline and regular time intervals during and after the infusion, over a period of 35 minutes.