# The effect of opioids on the light-off pupillary reflex

## TL;DR

This study shows that opioids like remifentanil strongly suppress the light-off pupillary reflex, a simple and intuitive measure that could help assess opioid effects and risk of respiratory depression.

## Contribution

The study identifies the light-off reflex as a novel, portable, and intuitive indicator of opioid effect and respiratory depression risk.

## Key findings

- Remifentanil reduced the light-off reflex and pupillary unrest by over 85%.
- The light-off reflex and pupillary unrest provided equivalent estimates of opioid effect and respiratory depression risk.
- The pupillary light reflex (NPi) was not affected by opioids.

## Abstract

We examined the relationship between modeled opioid concentration and quantitative pupillary measures during remifentanil infusion sequences with particular attention to the “light-off” (LO) reflex.

Ten volunteer subjects were recruited to undergo two 10-min remifentanil infusion protocols. Pupillary unrest in ambient light (PUAL) and LO were measured at baseline and every 2.5 min during the first 10-min infusion–25-min recovery sequence, and after a wash-out period, the Neurological Pupillary index (NPi) and LO were measured during an identical infusion–recovery sequence. We tested proportional change in each parameter from baseline as indicators of dynamic opioid effect.

On average, remifentanil decreased both LO dilation and PUAL by > 85%, decreased pupil diameter by > 48%, but did not significantly alter the NPi. Hypoxia occurred in 15/16 sequences. LO and PUAL both showed excellent discrimination between high-toxic versus zero-moderate opioid effect. In contrast to PUAL and LO, the scaled pupillary light reflex measurement (NPi) was not altered by opioids.

LO and PUAL were robust indicators of opioid effect and provided equivalent estimates of respiratory depression risk in our healthy awake subjects. Compared with PUAL, LO offers the advantage of being intuitive and easily derived at the bedside without need for specialized software.

Measurement of the pupillary LO reflex with a portable pupillometer provides a simple, discriminating measure of opioid effect.

Remifentanil blocks the pupillary LO reflex.

The online version contains supplementary material available at 10.1186/s44158-026-00340-8.

The effect of a toxic dose of remifentanil on the pupillary “light-off” reflex was studied in 10 volunteers.Given in a dose that produced apnea, the light-off reflex was suppressed over 85% compared to baseline.The pupillary light reflex was not changed by the drug.

The effect of a toxic dose of remifentanil on the pupillary “light-off” reflex was studied in 10 volunteers.

Given in a dose that produced apnea, the light-off reflex was suppressed over 85% compared to baseline.

The pupillary light reflex was not changed by the drug.

The online version contains supplementary material available at 10.1186/s44158-026-00340-8.