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We investigated the effect of opioids on pupillary size and dilation velocity in the pupillary light reflex in critically ill patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This is a sub\u2010study on 55 patients from a prospective observational study acutely admitted to an ICU. All patients had daily blood samples and pupillary light reflex measurements. Blood samples were analyzed for opioids using mass spectrometry. Linear mixed models were used to estimate the possible association for each detected opioid to pupillary size and dilation velocity in the pupillary light reflex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The pupil size before a light stimulus was closely associated to the dilation velocity after the light stimulus. The increase in the dilation velocity was 0.2\u2009mm\/s per 1\u2009mm increase in pupil diameter before the light stimulus, 95% confidence interval [0.2\u20130.3], <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001. Presence of fentanyl was associated with a smaller pupil size and a slower pupillary dilation velocity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The presence of fentanyl in blood samples from a mixed ICU population is associated with a slower pupillary dilation velocity in a concentration\u2010dependent matter.<\/jats:p><\/jats:sec><jats:sec><jats:title>Editorial Comment<\/jats:title><jats:p>This study assesses the relation of observed opioid levels and light reflex pupillary size speed of change in an ICU cohort where there can be multiple classes of drugs present which influence autonomic nerve system function. Findings for different opioids, though most specifically fentanyl, show that opioid plasma concentrations have clear association with slower pupillary dilation velocity with light reflex response.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aas.70080","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T23:39:19Z","timestamp":1750721959000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Influence of Opioids on Pupil Initial Diameter and Pupillary Dilation Velocity in <scp>ICU<\/scp> Patients"],"prefix":"10.1111","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3504-3563","authenticated-orcid":false,"given":"Valdemar Oskar Ingemann","family":"S\u00f8rensen","sequence":"first","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Copenhagen University Hospital \u2013 North Zealand  Hilleroed Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stine","family":"Uhrenholt","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Copenhagen University Hospital \u2013 North Zealand  Hilleroed Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannik","family":"Stokholm","sequence":"additional","affiliation":[{"name":"Department of Neurology Copenhagen University Hospital \u2013 North Zealand  Hilleroed Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4953-0814","authenticated-orcid":false,"given":"Thomas","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Neurology Copenhagen University Hospital \u2013 North Zealand  Hilleroed Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6585-2659","authenticated-orcid":false,"given":"Morten Heiberg","family":"Bestle","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Copenhagen University Hospital \u2013 North Zealand  Hilleroed Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/psyp.12901"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics8010019"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000000384"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16\u201020785"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsycho.2018.01.010"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c140014"},{"key":"e_1_2_10_8_1","volume-title":"The Pupil: Anatomy, Physiology, and Clinical Applications","author":"Loewenfeld I. 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