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

University of California, San Francisco10 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

Conditions

Opioid Toxicity Pupillary Miosis Respiratory Depression

Interventions

Remifentanil HydrochlorideDRUG

Infusion of 0.2 µg/k/m for 5 minutes, the 0.3 µg/k/m for 5 minutes.

Pupillometry measurementDEVICE

Pupillary measurements were taken at baseline and every 2.5 minutes during the 10-minute infusion and 25-minute recovery period.

Eligibility

Sex: ALLMin age: 40 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Area Under the Time Concentration Curve (AUROC )

PUAL measured by pupillometer. PUAL at zero-moderate opioid concentration (\<1.8 ng/mL) versus high-toxic opioid concentration (\>2.5 ng/mL) were dichotomous classifiers. Receiver Operating Characteristic curve constructed, with AUROC reported

Time frame: Baseline, and every 2.5 minutes during 10-minute infusion and 25-minute recovery