Evidence map›Paper›PMID 33651243›Full record

ArticleJournal of clinical monitoring and computing2022

Pupillary unrest, opioid intensity, and the impact of environmental stimulation on respiratory depression.

Rachel Eshima McKay, Michael A Kohn, Merlin D Larson

2 registry-linked trialsOpen access · hybridAbstract read
In one paragraph

Article in Journal of clinical monitoring and computing, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04301895 phase1completednot on this map

Pupillary Unrest in Ambient Light, and Relationship to Opioid-Induced Respiratory Depression in Volunteers

TypeinterventionalSponsorUniversity of California, San FranciscoRan2019 to 2019Enrolled20ConditionsOpioid, Intoxication, Perception Disturbance (Acute), Acute Pain, Overdose of OpiateArmsContinuous conversational interaction, Remifentanil infusion
NCT05391555 phase2 / phase3completednot on this map

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

TypeinterventionalSponsorUniversity of California, San FranciscoRan2022 to 2023Enrolled10ConditionsOpioid Toxicity, Pupillary Miosis, Respiratory DepressionArmsRemifentanil Hydrochloride, Pupillometry measurement
3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Impact of age on PUAL as an indicator of opioid effect in adult subjects.Journal of clinical monitoring and computing · 2026
    Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Rachel Eshima McKayDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA, USA. rachel.eshima@ucsf.edu.ORCID 0000-0001-9019-0589
Michael A KohnDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
Merlin D LarsonProfessor Emeritus, Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA, USA.
University of California, San Francisco · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Opioid-induced respiratory depression (OIRD) confers significant morbidity, but its onset can be challenging to recognize. Pain or stimulation effects of conversation may mask or attenuate common clinical manifestations of OIRD. We asked whether pupillary unrest could provide an objective signal of opioid exposure, and whether this signal would be independent from the confounding influence of extrinsic stimulation. We conducted a cross-over trial of healthy volunteers using identical remifentanil infusions separated by a washout period; in both, pupillary unrest in ambient light (PUAL) was measured at 2.5-min intervals. During one infusion, investigators continuously engaged the subject in conversation, while in the other, a quiet environment was maintained; measures of respiratory depression were compared under each condition. We tested PUAL's relationship to estimated opioid concentration under quiet conditions, measured PUAL's discrimination of lower versus higher opioid exposure using receiver operating characteristic (ROC) analysis, and assessed the effect of stimulation on PUAL versus opioid using mixed effects regression. Respiratory depression occurred more frequently under quiet conditions (p < 0.0001). Under both conditions, PUAL declined significantly over the course of the remifentanil infusion and rose during recovery (p < 0.0001). PUAL showed excellent discrimination in distinguishing higher versus absent-moderate opioid exposure (AUROC = 0.957 [0.929 to 0.985]), but was unaffected by interactive versus quiet conditions (mean difference, interactive - quiet = - 0.007, 95% CI - 0.016 to 0.002). PUAL is a consistent indicator of opioid effect, and distinguishes higher opioid concentrations independently of the stimulating effects of conversational interaction. Under equivalent opioid exposure, conversational interaction delayed the onset and minimized the severity of OIRD.Clinical trial registration: NCT04301895.

Indexed as

Analgesics, OpioidRespiratory InsufficiencyHealthy VolunteersHumansPupilRemifentanilAnalgesics, OpioidRemifentanilInfrared pupillometryMonitoring drug effectsOpioid induced respiratory depressionOpioid intoxicationOpioid medicationOpioid related patient safetypupillary responses

Identifiers

PMID33651243
PMCPMC9123055
OpenAlexW3134781080

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.