Opioid Toxicity, Pupillary Miosis, Respiratory Depression
Conditions
Brief summary
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.
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.
Interventions
Infusion of 0.2 µg/k/m for 5 minutes, the 0.3 µg/k/m for 5 minutes.
DEVICEPupillometry measurement
Pupillary measurements were taken at baseline and every 2.5 minutes during the 10-minute infusion and 25-minute recovery period.
Sponsors
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 60 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Time Concentration Curve (AUROC ) | Baseline, and every 2.5 minutes during 10-minute infusion and 25-minute recovery | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Remifentanil Infusion and Recovery Participants underwent a 10-minute remifentanil infusion. Pupillary measures were taken a baseline and every 2.5 minutes during the 10-minute infusion and 25-minute recovery period.
Remifentanil Hydrochloride: Infusion of 0.2 µg/k/m for 5 minutes, the 0.3 µg/k/m for 5 minutes.
Pupillometry measurement: Pupillary measurements were taken at baseline and every 2.5 minutes during the 10-minute infusion and 25-minute recovery period. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Remifentanil Infusion and Recovery |
|---|---|
| Age, Customized Age 40-60 years | 10 Participants |
| Race/Ethnicity, Customized Asian/Pacific Islander | 3 Participants |
| Race/Ethnicity, Customized Black | 1 Participants |
| Race/Ethnicity, Customized Latinx | 2 Participants |
| Race/Ethnicity, Customized White European | 4 Participants |
| Region of Enrollment United States | 10 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remifentanil Infusion and Recovery | Area Under the Time Concentration Curve (AUROC ) | 0.9700 Probability |