Detection of opioid effect with pupillometry.

Rachel Eshima Mckay,Merlín D Larson

doi:10.1016/j.autneu.2021.102869

Rachel Eshima Mckay, Merlín D Larson

Open Access

https://doi.org/10.1016/j.autneu.2021.102869

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Abstract

Opioids produce pupillary constriction but their impact on pupillary unrest and the dynamic parameters of the pupillary light reflex have not been characterized. Given the increasing use of portable pupillometers for care of critically ill patients, it is important to distinguish between opioid effects on the pupil versus those that have been reported to arise from traumatic and ischemic brain insults. We undertook this study to determine which pupillary responses are most profoundly and consistently affected by a progressive infusion of remifentanil. We studied the effect of remifentanil on the pupil using two portable infrared pupillometers in 18 volunteers. One pupillometer measured pupillary unrest in ambient light (PUAL) and the other pupillometer measured neurological pupillary index (NPi), constriction velocity (CV), pupil diameter (PD), latency, and % reflex (% reflex) following a transient light flash. Remifentanil was administered at predetermined weight-adjusted rates to raise opioid effect site concentration up to a range known to produce respiratory depression and oxyhemoglobin desaturation, based on a previously published pharmacokinetic model. PUAL was ablated by remifentanil, declining 94±6% from baseline at the time of maximum drug effect. Other pupillary measurements decreased 50-65% from baseline. NPi was unchanged. At the time of oxyhemoglobin desaturation, deviations in PD, CV, and % reflex were widely scattered, whereas PUAL consistently approached zero. PUAL is a highly specific indicator of central opioid effect. As a non-invasive measure, it may provide useful data to clinicians who prescribe opioids.

Highlights

There is a continuing need for clinical measures to assess opioid ef fect (Lee et al, 2015; Overdyk et al, 2018)
Dynamic measurements including pupillary unrest, reflex amplitude (RA), constriction velocity (CV), and percent light reflex (% reflex) have been proposed as more precise measures of opioid effect compared to pupil diameter (PD) (Pickworth et al, 1989; Pickworth and Fudala, 1990; Bokoch et al, 2015; Kongsgaard and Hoiseth, 2019; McKay et al, 2018; Rollins et al, 2015)
All volunteers remained in verbal contact with the investigators, there was significant respiratory depression observed in all cases

Summary

Introduction

There is a continuing need for clinical measures to assess opioid ef fect (Lee et al, 2015; Overdyk et al, 2018). Within the past ten years portable infrared pupillometers that can measure the pupil in darkness have become available (Larson and Behrends, 2015). These devices can quantify pupillary unrest and several parameters of the light reflex waveform. Opioids have been shown to depress oscillatory motions of the pupil in awake subjects These oscillatory motions are referred to as pupillary unrest in ambient light (PUAL) and are thought to arise from opposing inhibitory and excitatory influences on the Edinger-Westphal (EW) nu cleus (Bokoch et al, 2015; Turnbull et al, 2017; Smith et al, 1970). As a non-invasive measure, it may provide useful data to clinicians who prescribe opioids

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