The Effect of Opioids on the Light Off Pupillary Reflex

The Effect of Opioids on the Light Off Pupillary Reflex | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Effect of Opioids on the Light Off Pupillary Reflex Rachel Eshima McKay, Merlín Dean Larson This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8089378/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Objective: We examined the relationship between modelled opioid concentration and quantitative pupillary measures during remifentanil infusion sequences with particular attention the “light off” (LO) reflex. Methods: Ten volunteer subjects were recruited to undergo two 10-minute remifentanil infusion protocols. Pupillary unrest in ambient light (PUAL) and LO were measured at baseline and every 2.5 minutes during the first 10-minute infusion 25-minute 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. Results: 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. Conclusion: 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. Significance: Measurement of the pupillary LO reflex with a portable pupillometer provides a simple, discriminating measure of opioid effect. Pupil opioids pupillometry neuromonitoring pupillary light re Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 21 Dec, 2025 Reviews received at journal 07 Dec, 2025 Reviews received at journal 01 Dec, 2025 Reviewers agreed at journal 01 Dec, 2025 Reviewers agreed at journal 01 Dec, 2025 Reviewers agreed at journal 30 Nov, 2025 Reviewers invited by journal 24 Nov, 2025 Submission checks completed at journal 24 Nov, 2025 First submitted to journal 20 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Reflex","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-anesthesia-analgesia-and-critical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Journal of Anesthesia, Analgesia and Critical Care](https://janesthanalgcritcare.biomedcentral.com/)","snPcode":"44158","submissionUrl":"https://submission.nature.com/new-submission/44158/3","title":"Journal of Anesthesia, Analgesia and Critical Care","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pupil, opioids, pupillometry, neuromonitoring, pupillary light re","lastPublishedDoi":"10.21203/rs.3.rs-8089378/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8089378/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eObjective: We examined the relationship between modelled opioid concentration and quantitative pupillary measures during remifentanil infusion sequences with particular attention the “light off” (LO) reflex.\u003c/p\u003e\n\u003cp\u003eMethods: Ten volunteer subjects were recruited to undergo two 10-minute remifentanil infusion protocols. Pupillary unrest in ambient light (PUAL) and LO were measured at baseline and every 2.5 minutes during the first 10-minute infusion 25-minute 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.\u003c/p\u003e\n\u003cp\u003eResults: On average, remifentanil decreased both LO dilation and PUAL by \u0026gt; 85%, decreased pupil diameter by \u0026gt; 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.\u003c/p\u003e\n\u003cp\u003eConclusion: 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.\u003c/p\u003e\n\u003cp\u003eSignificance: Measurement of the pupillary LO reflex with a portable pupillometer provides a simple, discriminating measure of opioid effect.\u003c/p\u003e","manuscriptTitle":"The Effect of Opioids on the Light Off Pupillary Reflex","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-28 12:20:24","doi":"10.21203/rs.3.rs-8089378/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-22T04:58:58+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-08T00:11:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-01T18:57:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"149233780277182913217169220167262057606","date":"2025-12-01T17:39:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"310913117495718196058918312006654852405","date":"2025-12-01T16:59:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"74726746127295497642264613629150973657","date":"2025-11-30T12:34:47+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-25T00:42:19+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-24T13:50:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Anesthesia, Analgesia and Critical Care","date":"2025-11-20T14:14:48+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-anesthesia-analgesia-and-critical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Journal of Anesthesia, Analgesia and Critical Care](https://janesthanalgcritcare.biomedcentral.com/)","snPcode":"44158","submissionUrl":"https://submission.nature.com/new-submission/44158/3","title":"Journal of Anesthesia, Analgesia and Critical Care","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"168356b6-5e38-4a89-a051-7fe6e0537184","owner":[],"postedDate":"November 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-01-09T09:54:05+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-28 12:20:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8089378","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8089378","identity":"rs-8089378","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}