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Pupillary unrest, opioid intensity, and the impact of environmental stimulation on respiratory depression
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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123055/ https://www.ncbi.nlm.nih.gov/pubmed/33651243 http://dx.doi.org/10.1007/s10877-021-00675-3 |
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author | McKay, Rachel Eshima Kohn, Michael A. Larson, Merlin D. |
author_facet | McKay, Rachel Eshima Kohn, Michael A. Larson, Merlin D. |
author_sort | McKay, Rachel Eshima |
collection | PubMed |
description | 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: NCT 04301895 |
format | Online Article Text |
id | pubmed-9123055 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-91230552022-05-22 Pupillary unrest, opioid intensity, and the impact of environmental stimulation on respiratory depression McKay, Rachel Eshima Kohn, Michael A. Larson, Merlin D. J Clin Monit Comput Original Research 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: NCT 04301895 Springer Netherlands 2021-03-02 2022 /pmc/articles/PMC9123055/ /pubmed/33651243 http://dx.doi.org/10.1007/s10877-021-00675-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Research McKay, Rachel Eshima Kohn, Michael A. Larson, Merlin D. Pupillary unrest, opioid intensity, and the impact of environmental stimulation on respiratory depression |
title | Pupillary unrest, opioid intensity, and the impact of environmental stimulation on respiratory depression |
title_full | Pupillary unrest, opioid intensity, and the impact of environmental stimulation on respiratory depression |
title_fullStr | Pupillary unrest, opioid intensity, and the impact of environmental stimulation on respiratory depression |
title_full_unstemmed | Pupillary unrest, opioid intensity, and the impact of environmental stimulation on respiratory depression |
title_short | Pupillary unrest, opioid intensity, and the impact of environmental stimulation on respiratory depression |
title_sort | pupillary unrest, opioid intensity, and the impact of environmental stimulation on respiratory depression |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123055/ https://www.ncbi.nlm.nih.gov/pubmed/33651243 http://dx.doi.org/10.1007/s10877-021-00675-3 |
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