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

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

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.

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.